Web Desc
Extracellular Matrix and Cardiovascular Remodeling
Organizer(s): Merry L. Lindsey and Thomas K. Borg
Date: January 23 - 28, 2011
Location: Granlibakken Tahoe, Tahoe City, CA, USA
Supported by the Directors' Fund
Summary of Meeting:
In response to normal growth as well as a variety of pathophysiological signals, the cardiovascular system undergoes a series of structural and functional adaptations, collectively known as remodeling, that are directed responses to both the initial stimulus and to feed-forward changes that result from the precipitating event. Remodeling is driven by the extracellular matrix (ECM) environment, in terms of altered ECM levels, composition, and function. The purpose of this meeting is to bring together researchers, clinicians, and pharmaceutical industry representatives to 1) focus on controversies and knowledge gaps that still prevent or limit therapeutic translation; 2) borrow from other fields (particularly cancer and skin wound healing) to gain insight into ECM functions; and 3) to offer direction and stimulate progress in cardiovascular ECM research.
Scholarship Deadline: September 23 2010
Discounted Abstract Deadline: September 23 2010
Abstract Deadline: October 26 2010
Discounted Registration Deadline: November 23 2010
We gratefully acknowledge additional support for this conference from:
Hatteras Instruments, Inc.Kent Scientific Corporation


Daisuke Yamamoto
We appreciate the organizations that provide Keystone Symposia with additional support, such as marketing and advertising:
Extracellular Matrix News
We gratefully acknowledge the generous grant for this conference provided by:

National Heart, Lung, and Blood Institute (NHLBI)
Grant No. 1R13HL104797-01
We appreciate the organizations that provide Keystone Symposia with additional support, such as marketing and advertising:

Click here to view more of these organizations
Special thanks to the following for their support of Keystone Symposia initiatives to increase participation at this meeting by scientists from underrepresented backgrounds:

Click here to view more of these organizations

Program

Sunday, January 23 | 3:00PM - 7:30PM
Registration
Room: Pre Function


Sunday, January 23 | 7:15PM - 8:30PM
Welcoming Remarks and Keynote Address
Room: Mountain/Lake

Speaker 2 of 2
Georg Ertl, Universitätsklinikum Würzburg, Germany
The Concept of Cardiac Wound Healing

Sunday, January 23 | 7:15PM - 8:30PM
Welcoming Remarks and Keynote Address
Room: Mountain/Lake

Speaker 1 of 2
* Merry L. Lindsey, University of Nebraska Medical Center., USA

Monday, January 24 | 7:00AM - 8:00AM
Breakfast
Room: Granhall


Monday, January 24 | 8:00AM - 11:15AM
What are the Dynamics and Functional Consequences of ECM in
Growth and Injury?

Room: Mountain/Lake
Using ECM changes to define mechanisms, versus using matrix changes as observational study end points, will provide direct translational applications for ECM targets. Proteolytic activity in the ECM involves a cascade of activities that can release and activate latent regulatory molecules such as growth factors, produce matrikines that stimulate cell signaling, and modify the environment to permit the cell growth and functional changes for a variety of cell types (e.g., myocytes, endothelial cells, fibroblasts). Matrix metalloproteinases (MMPs) appear to play a potentially significant role in this cascade by regulating ECM signaling, but is this only because MMPs are more studied than other protease families?
Speaker 8 of 8
Perla Ayala, University of California, San Francisco, USA
Short Talk: Polymer Microstructures Influence Extracellular Matrix Remodeling in vitro and in vivo

Monday, January 24 | 8:00AM - 11:15AM
What are the Dynamics and Functional Consequences of ECM in
Growth and Injury?

Room: Mountain/Lake
Using ECM changes to define mechanisms, versus using matrix changes as observational study end points, will provide direct translational applications for ECM targets. Proteolytic activity in the ECM involves a cascade of activities that can release and activate latent regulatory molecules such as growth factors, produce matrikines that stimulate cell signaling, and modify the environment to permit the cell growth and functional changes for a variety of cell types (e.g., myocytes, endothelial cells, fibroblasts). Matrix metalloproteinases (MMPs) appear to play a potentially significant role in this cascade by regulating ECM signaling, but is this only because MMPs are more studied than other protease families?
Speaker 7 of 8
Anne A. Knowlton, University of California, Davis, USA
Estrogen, Aging and the Extracellular Matrix

Monday, January 24 | 8:00AM - 11:15AM
What are the Dynamics and Functional Consequences of ECM in
Growth and Injury?

Room: Mountain/Lake
Using ECM changes to define mechanisms, versus using matrix changes as observational study end points, will provide direct translational applications for ECM targets. Proteolytic activity in the ECM involves a cascade of activities that can release and activate latent regulatory molecules such as growth factors, produce matrikines that stimulate cell signaling, and modify the environment to permit the cell growth and functional changes for a variety of cell types (e.g., myocytes, endothelial cells, fibroblasts). Matrix metalloproteinases (MMPs) appear to play a potentially significant role in this cascade by regulating ECM signaling, but is this only because MMPs are more studied than other protease families?
Speaker 6 of 8
George E. Davis, University of Missouri School of Medicine, USA
ECM Remodeling Events Controlling Vascular Morphogenesis

Monday, January 24 | 8:00AM - 11:15AM
What are the Dynamics and Functional Consequences of ECM in
Growth and Injury?

Room: Mountain/Lake
Using ECM changes to define mechanisms, versus using matrix changes as observational study end points, will provide direct translational applications for ECM targets. Proteolytic activity in the ECM involves a cascade of activities that can release and activate latent regulatory molecules such as growth factors, produce matrikines that stimulate cell signaling, and modify the environment to permit the cell growth and functional changes for a variety of cell types (e.g., myocytes, endothelial cells, fibroblasts). Matrix metalloproteinases (MMPs) appear to play a potentially significant role in this cascade by regulating ECM signaling, but is this only because MMPs are more studied than other protease families?
Speaker 5 of 8
W. Matthijs Blankesteijn, Maastricht University, Netherlands
Short Talk: Increased Myofibroblast Numbers in the Infarct Area can Prevent Ventricular Dilatation after Infarction

Monday, January 24 | 8:00AM - 11:15AM
What are the Dynamics and Functional Consequences of ECM in
Growth and Injury?

Room: Mountain/Lake
Using ECM changes to define mechanisms, versus using matrix changes as observational study end points, will provide direct translational applications for ECM targets. Proteolytic activity in the ECM involves a cascade of activities that can release and activate latent regulatory molecules such as growth factors, produce matrikines that stimulate cell signaling, and modify the environment to permit the cell growth and functional changes for a variety of cell types (e.g., myocytes, endothelial cells, fibroblasts). Matrix metalloproteinases (MMPs) appear to play a potentially significant role in this cascade by regulating ECM signaling, but is this only because MMPs are more studied than other protease families?
Speaker 4 of 8
Neil A. Turner, University of Leeds, UK
Cardiac Fibroblast Roles in ECM Turnover

Monday, January 24 | 8:00AM - 11:15AM
What are the Dynamics and Functional Consequences of ECM in
Growth and Injury?

Room: Mountain/Lake
Using ECM changes to define mechanisms, versus using matrix changes as observational study end points, will provide direct translational applications for ECM targets. Proteolytic activity in the ECM involves a cascade of activities that can release and activate latent regulatory molecules such as growth factors, produce matrikines that stimulate cell signaling, and modify the environment to permit the cell growth and functional changes for a variety of cell types (e.g., myocytes, endothelial cells, fibroblasts). Matrix metalloproteinases (MMPs) appear to play a potentially significant role in this cascade by regulating ECM signaling, but is this only because MMPs are more studied than other protease families?
Speaker 3 of 8
Thomas K. Borg, Medical University of South Carolina, USA
Dynamics of ECM Turnover

Monday, January 24 | 8:00AM - 11:15AM
What are the Dynamics and Functional Consequences of ECM in
Growth and Injury?

Room: Mountain/Lake
Using ECM changes to define mechanisms, versus using matrix changes as observational study end points, will provide direct translational applications for ECM targets. Proteolytic activity in the ECM involves a cascade of activities that can release and activate latent regulatory molecules such as growth factors, produce matrikines that stimulate cell signaling, and modify the environment to permit the cell growth and functional changes for a variety of cell types (e.g., myocytes, endothelial cells, fibroblasts). Matrix metalloproteinases (MMPs) appear to play a potentially significant role in this cascade by regulating ECM signaling, but is this only because MMPs are more studied than other protease families?
Speaker 2 of 8
* Merry L. Lindsey, University of Nebraska Medical Center., USA

Monday, January 24 | 8:00AM - 11:15AM
What are the Dynamics and Functional Consequences of ECM in
Growth and Injury?

Room: Mountain/Lake
Using ECM changes to define mechanisms, versus using matrix changes as observational study end points, will provide direct translational applications for ECM targets. Proteolytic activity in the ECM involves a cascade of activities that can release and activate latent regulatory molecules such as growth factors, produce matrikines that stimulate cell signaling, and modify the environment to permit the cell growth and functional changes for a variety of cell types (e.g., myocytes, endothelial cells, fibroblasts). Matrix metalloproteinases (MMPs) appear to play a potentially significant role in this cascade by regulating ECM signaling, but is this only because MMPs are more studied than other protease families?
Speaker 1 of 8
* Georg Ertl, Universitätsklinikum Würzburg, Germany

Monday, January 24 | 9:20AM - 9:40AM
Coffee Break
Room: Pre Function


Monday, January 24 | 11:15AM - 1:00PM
Poster Setup
Room: Bay


Monday, January 24 | 11:15AM - 11:15AM
On Own for Lunch and Recreation


Monday, January 24 | 1:00PM - 10:00PM
Poster Viewing
Room: Bay


Monday, January 24 | 2:30PM - 4:30PM
Workshop 1: Small Group Meeting with Trainees
Room: Mountain/Lake
The organizers of this Keystone Symposia meeting plan to designate two hours this afternoon for speakers to meet with graduate students, post doctoral fellows and junior faculty to discuss a variety of topics including grant writing and avenues to find support, faculty positions (how to get one and how to thrive in one), how to maximize efficiency (turning a grant introduction into a review article), peer mentoring, etc.

Monday, January 24 | 4:30PM - 5:00PM
Coffee Available
Room: Pre Function


Monday, January 24 | 5:00PM - 7:00PM
Variety of ECM Components: What Do They All Do? Part I
Room: Mountain/Lake
In remodeling as well as growth, many ECM components serve as substrates for various proteases. While the best investigated protease family has been the MMPs, a complete spatiotemporal profile of MMP changes during disease progression and a full catalogue of MMP substrates processed during disease progression have not been documented. MMP processing of substrate is an initial event, and fluctuation in various signaling events caused by differences in substrate availability affect downstream function of fibroblasts, myocytes and vasculature, in addition to inflammatory cells in certain cases. Regulation at the level of the substrate provides spatial and temporal regulation of MMP activity. We still, however, do not have a good sense of whether primary MMP roles in cardiovascular remodeling occur through ECM or non-ECM substrate processing. Cooperation between the parenchyma, vasculature and mesenchymal cells is critical but what are the signals involved in this communication?
Speaker 6 of 6
J. Gary Meszaros, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, USA
Type VI Collagen Alters Cardiac Fibroblast Function and Post-MI Remodeling

Monday, January 24 | 5:00PM - 7:00PM
Variety of ECM Components: What Do They All Do? Part I
Room: Mountain/Lake
In remodeling as well as growth, many ECM components serve as substrates for various proteases. While the best investigated protease family has been the MMPs, a complete spatiotemporal profile of MMP changes during disease progression and a full catalogue of MMP substrates processed during disease progression have not been documented. MMP processing of substrate is an initial event, and fluctuation in various signaling events caused by differences in substrate availability affect downstream function of fibroblasts, myocytes and vasculature, in addition to inflammatory cells in certain cases. Regulation at the level of the substrate provides spatial and temporal regulation of MMP activity. We still, however, do not have a good sense of whether primary MMP roles in cardiovascular remodeling occur through ECM or non-ECM substrate processing. Cooperation between the parenchyma, vasculature and mesenchymal cells is critical but what are the signals involved in this communication?
Speaker 5 of 6
Amy D. Bradshaw, Medical University of South Carolina, USA
The Role of SPARC in Cardiac Hypertrophy: A Matricellular Regulator of Cardiac Collagen

Monday, January 24 | 5:00PM - 7:00PM
Variety of ECM Components: What Do They All Do? Part I
Room: Mountain/Lake
In remodeling as well as growth, many ECM components serve as substrates for various proteases. While the best investigated protease family has been the MMPs, a complete spatiotemporal profile of MMP changes during disease progression and a full catalogue of MMP substrates processed during disease progression have not been documented. MMP processing of substrate is an initial event, and fluctuation in various signaling events caused by differences in substrate availability affect downstream function of fibroblasts, myocytes and vasculature, in addition to inflammatory cells in certain cases. Regulation at the level of the substrate provides spatial and temporal regulation of MMP activity. We still, however, do not have a good sense of whether primary MMP roles in cardiovascular remodeling occur through ECM or non-ECM substrate processing. Cooperation between the parenchyma, vasculature and mesenchymal cells is critical but what are the signals involved in this communication?
Speaker 4 of 6
Patrick Collier, University College, Dublin Conway Institute, Ireland
Short Talk: Biomechanical Properties of Major Collagen Fiber Subtypes 1 & 3 in Human Myocardial Tissue

Monday, January 24 | 5:00PM - 7:00PM
Variety of ECM Components: What Do They All Do? Part I
Room: Mountain/Lake
In remodeling as well as growth, many ECM components serve as substrates for various proteases. While the best investigated protease family has been the MMPs, a complete spatiotemporal profile of MMP changes during disease progression and a full catalogue of MMP substrates processed during disease progression have not been documented. MMP processing of substrate is an initial event, and fluctuation in various signaling events caused by differences in substrate availability affect downstream function of fibroblasts, myocytes and vasculature, in addition to inflammatory cells in certain cases. Regulation at the level of the substrate provides spatial and temporal regulation of MMP activity. We still, however, do not have a good sense of whether primary MMP roles in cardiovascular remodeling occur through ECM or non-ECM substrate processing. Cooperation between the parenchyma, vasculature and mesenchymal cells is critical but what are the signals involved in this communication?
Speaker 3 of 6
Troy A. Baudino, Texas A&M Health Science Center, USA
The Extracellular Matrix; Where Does It Come From?

Monday, January 24 | 5:00PM - 7:00PM
Variety of ECM Components: What Do They All Do? Part I
Room: Mountain/Lake
In remodeling as well as growth, many ECM components serve as substrates for various proteases. While the best investigated protease family has been the MMPs, a complete spatiotemporal profile of MMP changes during disease progression and a full catalogue of MMP substrates processed during disease progression have not been documented. MMP processing of substrate is an initial event, and fluctuation in various signaling events caused by differences in substrate availability affect downstream function of fibroblasts, myocytes and vasculature, in addition to inflammatory cells in certain cases. Regulation at the level of the substrate provides spatial and temporal regulation of MMP activity. We still, however, do not have a good sense of whether primary MMP roles in cardiovascular remodeling occur through ECM or non-ECM substrate processing. Cooperation between the parenchyma, vasculature and mesenchymal cells is critical but what are the signals involved in this communication?
Speaker 2 of 6
* W. Matthijs Blankesteijn, Maastricht University, Netherlands

Monday, January 24 | 5:00PM - 7:00PM
Variety of ECM Components: What Do They All Do? Part I
Room: Mountain/Lake
In remodeling as well as growth, many ECM components serve as substrates for various proteases. While the best investigated protease family has been the MMPs, a complete spatiotemporal profile of MMP changes during disease progression and a full catalogue of MMP substrates processed during disease progression have not been documented. MMP processing of substrate is an initial event, and fluctuation in various signaling events caused by differences in substrate availability affect downstream function of fibroblasts, myocytes and vasculature, in addition to inflammatory cells in certain cases. Regulation at the level of the substrate provides spatial and temporal regulation of MMP activity. We still, however, do not have a good sense of whether primary MMP roles in cardiovascular remodeling occur through ECM or non-ECM substrate processing. Cooperation between the parenchyma, vasculature and mesenchymal cells is critical but what are the signals involved in this communication?
Speaker 1 of 6
* Thomas K. Borg, Medical University of South Carolina, USA

Monday, January 24 | 7:00PM - 8:00PM
Dinner
Room: Granhall


Monday, January 24 | 8:00PM - 10:00PM
Poster Session 1
Room: Bay


Monday, January 24 | 8:00PM - 9:00PM
Social Hour
Room: Bay


Tuesday, January 25 | 7:00AM - 8:00AM
Breakfast
Room: Granhall


Tuesday, January 25 | 8:00AM - 11:15AM
Variety of ECM Components: What Do They All Do? Part II
Room: Mountain/Lake

Speaker 1 of 8
* Troy A. Baudino, Texas A&M Health Science Center, USA

Tuesday, January 25 | 8:00AM - 11:15AM
Variety of ECM Components: What Do They All Do? Part II
Room: Mountain/Lake

Speaker 2 of 8
* J. Gary Meszaros, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, USA

Tuesday, January 25 | 8:00AM - 11:15AM
Variety of ECM Components: What Do They All Do? Part II
Room: Mountain/Lake

Speaker 3 of 8
Krishna Singh, East Tennessee State University, USA
Osteopontin: Role in Extracellular Matrix Deposition and Mycocardial Remodeling

Tuesday, January 25 | 8:00AM - 11:15AM
Variety of ECM Components: What Do They All Do? Part II
Room: Mountain/Lake

Speaker 4 of 8
Kevin J. McCarthy, Louisiana State University Health Science Center, USA
Basement Membrane Integrity: A Molecular Genetic Approach to Probing Structure and Function

Tuesday, January 25 | 8:00AM - 11:15AM
Variety of ECM Components: What Do They All Do? Part II
Room: Mountain/Lake

Speaker 5 of 8
Bridget Leonard, University of Auckland, New Zealand
Short Talk: Does this Collagen Make My Heart Look Big? Quantifying Regional Cardiac Function and Collagen Organization following Myocardial Infarction

Tuesday, January 25 | 8:00AM - 11:15AM
Variety of ECM Components: What Do They All Do? Part II
Room: Mountain/Lake

Speaker 6 of 8
Edie C. Goldsmith, University of South Carolina, USA
Short Talk: Using Gold Nanorods to Modulate Cardiac Fibroblast Behavior and the Mechanical Properties of Collagen Matrices

Tuesday, January 25 | 8:00AM - 11:15AM
Variety of ECM Components: What Do They All Do? Part II
Room: Mountain/Lake

Speaker 7 of 8
Pamela A. Lucchesi, Research Institute at Nationwide Children's Hospital, USA
Extracellular Matrix Remodeling during the Progression of Volume Overload-Induced Heart Failure

Tuesday, January 25 | 8:00AM - 11:15AM
Variety of ECM Components: What Do They All Do? Part II
Room: Mountain/Lake

Speaker 8 of 8
Jeffrey W. Holmes, University of Virginia, USA
Contribution of Extracellular Matrix to the Mechanical Properties of the Heart

Tuesday, January 25 | 9:20AM - 9:40AM
Coffee Break
Room: Pre Function


Tuesday, January 25 | 11:15AM - 1:00PM
Poster Setup
Room: Bay


Tuesday, January 25 | 11:15AM - 11:15AM
On Own for Lunch and Recreation


Tuesday, January 25 | 1:00PM - 10:00PM
Poster Viewing
Room: Bay


Tuesday, January 25 | 4:30PM - 5:00PM
Coffee Available
Room: Pre Function


Tuesday, January 25 | 5:00PM - 7:00PM
What are the Roles of Proteases in Growth and Injury of the
Myocardium?

Room: Mountain/Lake
A variety of proteases and their inhibitors are involved in the normal turnover of ECM components in normal growth as well as in injury. These proteases include serine proteases uPA and tPA, the matrix metalloproteases MMPs) and ADAMS. Most studies have focused on the MMPs yet the dynamics (interactions) of the various proteases appears to be important in the sequence of response to injury. In addition, while a multitude of studies monitor MMP levels during the development of cardiovascular disease, few highlight that MMP regulation of ECM is a cascade that involves MMPs as an input to the system and not merely a read-out parameter. Can we use cancer models to guide cardiovascular research?

TIMP roles and other protease inhibitors also need further evaluation. Pro-TIMP-1 binds pro-MMP-9 and prevents MMP-9 homodimerization and prevents cell migration without MMP activation, which suggests pro-MMP-9 is not merely a pre-active enzyme. In addition, several TIMPs have activities apart of MMP inhibition, including growth factor roles. Given that so many MMPs increase during injury and pathology, whether the primary level of regulation of net ECM turnover occurs at the level of the TIMPs has not been examined.

Speaker 1 of 6
* Pamela A. Lucchesi, Research Institute at Nationwide Children's Hospital, USA

Tuesday, January 25 | 5:00PM - 7:00PM
What are the Roles of Proteases in Growth and Injury of the
Myocardium?

Room: Mountain/Lake
A variety of proteases and their inhibitors are involved in the normal turnover of ECM components in normal growth as well as in injury. These proteases include serine proteases uPA and tPA, the matrix metalloproteases MMPs) and ADAMS. Most studies have focused on the MMPs yet the dynamics (interactions) of the various proteases appears to be important in the sequence of response to injury. In addition, while a multitude of studies monitor MMP levels during the development of cardiovascular disease, few highlight that MMP regulation of ECM is a cascade that involves MMPs as an input to the system and not merely a read-out parameter. Can we use cancer models to guide cardiovascular research?

TIMP roles and other protease inhibitors also need further evaluation. Pro-TIMP-1 binds pro-MMP-9 and prevents MMP-9 homodimerization and prevents cell migration without MMP activation, which suggests pro-MMP-9 is not merely a pre-active enzyme. In addition, several TIMPs have activities apart of MMP inhibition, including growth factor roles. Given that so many MMPs increase during injury and pathology, whether the primary level of regulation of net ECM turnover occurs at the level of the TIMPs has not been examined.

Speaker 2 of 6
* Bridget Leonard, University of Auckland, New Zealand

Tuesday, January 25 | 5:00PM - 7:00PM
What are the Roles of Proteases in Growth and Injury of the
Myocardium?

Room: Mountain/Lake
A variety of proteases and their inhibitors are involved in the normal turnover of ECM components in normal growth as well as in injury. These proteases include serine proteases uPA and tPA, the matrix metalloproteases MMPs) and ADAMS. Most studies have focused on the MMPs yet the dynamics (interactions) of the various proteases appears to be important in the sequence of response to injury. In addition, while a multitude of studies monitor MMP levels during the development of cardiovascular disease, few highlight that MMP regulation of ECM is a cascade that involves MMPs as an input to the system and not merely a read-out parameter. Can we use cancer models to guide cardiovascular research?

TIMP roles and other protease inhibitors also need further evaluation. Pro-TIMP-1 binds pro-MMP-9 and prevents MMP-9 homodimerization and prevents cell migration without MMP activation, which suggests pro-MMP-9 is not merely a pre-active enzyme. In addition, several TIMPs have activities apart of MMP inhibition, including growth factor roles. Given that so many MMPs increase during injury and pathology, whether the primary level of regulation of net ECM turnover occurs at the level of the TIMPs has not been examined.

Speaker 3 of 6
Ren-Ke Li, Toronto General Hospital, Canada
Cell and Gene Therapy Preserves Matrix Homeostasis: A Novel Paracrine Mechanism Preventing Detrimental Myocardial Matrix Modulation

Tuesday, January 25 | 5:00PM - 7:00PM
What are the Roles of Proteases in Growth and Injury of the
Myocardium?

Room: Mountain/Lake
A variety of proteases and their inhibitors are involved in the normal turnover of ECM components in normal growth as well as in injury. These proteases include serine proteases uPA and tPA, the matrix metalloproteases MMPs) and ADAMS. Most studies have focused on the MMPs yet the dynamics (interactions) of the various proteases appears to be important in the sequence of response to injury. In addition, while a multitude of studies monitor MMP levels during the development of cardiovascular disease, few highlight that MMP regulation of ECM is a cascade that involves MMPs as an input to the system and not merely a read-out parameter. Can we use cancer models to guide cardiovascular research?

TIMP roles and other protease inhibitors also need further evaluation. Pro-TIMP-1 binds pro-MMP-9 and prevents MMP-9 homodimerization and prevents cell migration without MMP activation, which suggests pro-MMP-9 is not merely a pre-active enzyme. In addition, several TIMPs have activities apart of MMP inhibition, including growth factor roles. Given that so many MMPs increase during injury and pathology, whether the primary level of regulation of net ECM turnover occurs at the level of the TIMPs has not been examined.

Speaker 4 of 6
Rolf K. Reed, University of Bergen, Norway
Connective Tissue Remodeling: Role of Edena and Fluid Dynamics

Tuesday, January 25 | 5:00PM - 7:00PM
What are the Roles of Proteases in Growth and Injury of the
Myocardium?

Room: Mountain/Lake
A variety of proteases and their inhibitors are involved in the normal turnover of ECM components in normal growth as well as in injury. These proteases include serine proteases uPA and tPA, the matrix metalloproteases MMPs) and ADAMS. Most studies have focused on the MMPs yet the dynamics (interactions) of the various proteases appears to be important in the sequence of response to injury. In addition, while a multitude of studies monitor MMP levels during the development of cardiovascular disease, few highlight that MMP regulation of ECM is a cascade that involves MMPs as an input to the system and not merely a read-out parameter. Can we use cancer models to guide cardiovascular research?

TIMP roles and other protease inhibitors also need further evaluation. Pro-TIMP-1 binds pro-MMP-9 and prevents MMP-9 homodimerization and prevents cell migration without MMP activation, which suggests pro-MMP-9 is not merely a pre-active enzyme. In addition, several TIMPs have activities apart of MMP inhibition, including growth factor roles. Given that so many MMPs increase during injury and pathology, whether the primary level of regulation of net ECM turnover occurs at the level of the TIMPs has not been examined.

Speaker 5 of 6
David G. Greenhouse, New York University School of Medicine, USA
Short Talk: Mitral Valve Prolapse is Associated with Altered Extracellular Matrix Gene Expression

Tuesday, January 25 | 5:00PM - 7:00PM
What are the Roles of Proteases in Growth and Injury of the
Myocardium?

Room: Mountain/Lake
A variety of proteases and their inhibitors are involved in the normal turnover of ECM components in normal growth as well as in injury. These proteases include serine proteases uPA and tPA, the matrix metalloproteases MMPs) and ADAMS. Most studies have focused on the MMPs yet the dynamics (interactions) of the various proteases appears to be important in the sequence of response to injury. In addition, while a multitude of studies monitor MMP levels during the development of cardiovascular disease, few highlight that MMP regulation of ECM is a cascade that involves MMPs as an input to the system and not merely a read-out parameter. Can we use cancer models to guide cardiovascular research?

TIMP roles and other protease inhibitors also need further evaluation. Pro-TIMP-1 binds pro-MMP-9 and prevents MMP-9 homodimerization and prevents cell migration without MMP activation, which suggests pro-MMP-9 is not merely a pre-active enzyme. In addition, several TIMPs have activities apart of MMP inhibition, including growth factor roles. Given that so many MMPs increase during injury and pathology, whether the primary level of regulation of net ECM turnover occurs at the level of the TIMPs has not been examined.

Speaker 6 of 6
Daisuke Yamamoto, Osaka Medical College, Japan
ACE Inhibitors Block MMP-9 Activity: New Tricks for Old Dogs

Tuesday, January 25 | 7:00PM - 8:00PM
Dinner
Room: Granhall


Tuesday, January 25 | 8:00PM - 10:00PM
Poster Session 2
Room: Bay


Tuesday, January 25 | 8:00PM - 9:00PM
Social Hour
Room: Bay


Wednesday, January 26 | 7:00AM - 8:00AM
Breakfast
Room: Granhall


Wednesday, January 26 | 8:00AM - 11:15AM
Is Inflammation a Key Component Here? Part I
Room: Mountain/Lake
Inflammation is a carefully controlled set of reactions that involves a wide variety of cellular and ECM events. This topic will investigate how inflammatory components such as cytokines and chemokines regulate ECM responses.
Speaker 1 of 8
* Edie C. Goldsmith, University of South Carolina, USA

Wednesday, January 26 | 8:00AM - 11:15AM
Is Inflammation a Key Component Here? Part I
Room: Mountain/Lake
Inflammation is a carefully controlled set of reactions that involves a wide variety of cellular and ECM events. This topic will investigate how inflammatory components such as cytokines and chemokines regulate ECM responses.
Speaker 2 of 8
Dirk Westermann, Charité–Universitätsmedizin Berlin, Germany
Immunomodulation and Matrix Metalloproteinases in Viral Myocarditis

Wednesday, January 26 | 8:00AM - 11:15AM
Is Inflammation a Key Component Here? Part I
Room: Mountain/Lake
Inflammation is a carefully controlled set of reactions that involves a wide variety of cellular and ECM events. This topic will investigate how inflammatory components such as cytokines and chemokines regulate ECM responses.
Speaker 3 of 8
* Rolf K. Reed, University of Bergen, Norway

Wednesday, January 26 | 8:00AM - 11:15AM
Is Inflammation a Key Component Here? Part I
Room: Mountain/Lake
Inflammation is a carefully controlled set of reactions that involves a wide variety of cellular and ECM events. This topic will investigate how inflammatory components such as cytokines and chemokines regulate ECM responses.
Speaker 4 of 8
Suresh C. Tyagi, University of Louisville School of Medicine, USA
Juxtacrine Endothelial Myocyte Matrix in Cardiac Remodeling: A Translational Approach & H2S as Cardioprotection

Wednesday, January 26 | 8:00AM - 11:15AM
Is Inflammation a Key Component Here? Part I
Room: Mountain/Lake
Inflammation is a carefully controlled set of reactions that involves a wide variety of cellular and ECM events. This topic will investigate how inflammatory components such as cytokines and chemokines regulate ECM responses.
Speaker 5 of 8
Linus Malm, Umea University, Sweden
Short Talk: Size Determination of Hyaluronan using DLS and GEMMA

Wednesday, January 26 | 8:00AM - 11:15AM
Is Inflammation a Key Component Here? Part I
Room: Mountain/Lake
Inflammation is a carefully controlled set of reactions that involves a wide variety of cellular and ECM events. This topic will investigate how inflammatory components such as cytokines and chemokines regulate ECM responses.
Speaker 6 of 8
Sandra B. Haudek, Baylor College of Medicine, USA
Cardiac Fibroblast Precursor Cell Differentiation

Wednesday, January 26 | 8:00AM - 11:15AM
Is Inflammation a Key Component Here? Part I
Room: Mountain/Lake
Inflammation is a carefully controlled set of reactions that involves a wide variety of cellular and ECM events. This topic will investigate how inflammatory components such as cytokines and chemokines regulate ECM responses.
Speaker 7 of 8
Helene Skjøt-Arkil, Nordic Bioscience, Denmark
Short Talk: Human Macrophage Foam Cells Generate a Specific Proteolytic Fragment of CRP - A Novel Method for Evaluation of Macrophage Foam Cell Activity

Wednesday, January 26 | 8:00AM - 11:15AM
Is Inflammation a Key Component Here? Part I
Room: Mountain/Lake
Inflammation is a carefully controlled set of reactions that involves a wide variety of cellular and ECM events. This topic will investigate how inflammatory components such as cytokines and chemokines regulate ECM responses.
Speaker 8 of 8
Yan Ni, Merck & Co., Inc., USA
Extracellular Matrix Protein as Biomarker for Cardiac Remodeling: From a Drug Development View

Wednesday, January 26 | 9:20AM - 9:40AM
Coffee Break
Room: Pre Function


Wednesday, January 26 | 11:15AM - 1:00PM
Poster Setup
Room: Bay


Wednesday, January 26 | 11:15AM - 11:15AM
On Own for Lunch and Recreation


Wednesday, January 26 | 1:00PM - 10:00PM
Poster Viewing
Room: Bay


Wednesday, January 26 | 2:30PM - 4:30PM
Workshop 2: Small Group Meeting with Trainees
Room: Mountain/Lake
The organizers of this Keystone Symposia meeting plan to designate two hours this afternoon for speakers to meet with graduate students, post doctoral fellows and junior faculty to discuss a variety of topics including grant writing and avenues to find support, faculty positions (how to get one and how to thrive in one), how to maximize efficiency (turning a grant introduction into a review article), peer mentoring, etc.

Wednesday, January 26 | 4:30PM - 5:00PM
Coffee Available
Room: Pre Function


Wednesday, January 26 | 5:00PM - 7:00PM
Is Inflammation a Key Component Here? Part II
Room: Mountain/Lake

Speaker 1 of 6
* Sandra B. Haudek, Baylor College of Medicine, USA

Wednesday, January 26 | 5:00PM - 7:00PM
Is Inflammation a Key Component Here? Part II
Room: Mountain/Lake

Speaker 2 of 6
* Dirk Westermann, Charité–Universitätsmedizin Berlin, Germany

Wednesday, January 26 | 5:00PM - 7:00PM
Is Inflammation a Key Component Here? Part II
Room: Mountain/Lake

Speaker 3 of 6
Ferdinando Mannello, University Carlo Bo of Urbino, Italy
Cross-Talk between Matrix Metalloproteinases and Glycosaminoglycans in Vascular Remodeling: Who Rules Who?


Wednesday, January 26 | 5:00PM - 7:00PM
Is Inflammation a Key Component Here? Part II
Room: Mountain/Lake

Speaker 4 of 6
Marielle Scherrer-Crosbie, Massachusetts General Hospital, USA
Ventricular Remodeling and Function: Insights using Mouse Echocardiography.


Wednesday, January 26 | 5:00PM - 7:00PM
Is Inflammation a Key Component Here? Part II
Room: Mountain/Lake

Speaker 5 of 6
Stephanie Feldman Majkut, University of Pennsylvania, USA
Short Talk: Elasticity of Developing Cardiac Tissue and its Influence on Early Cardiomyocyte Beating

Wednesday, January 26 | 5:00PM - 7:00PM
Is Inflammation a Key Component Here? Part II
Room: Mountain/Lake

Speaker 6 of 6
Yufang Jin, University of Texas at San Antonio, USA
Modeling and Analysis of Left Ventricular Remodeling: Integration of Experimental and Computational Approaches

Wednesday, January 26 | 7:00PM - 8:00PM
Dinner
Room: Granhall


Wednesday, January 26 | 8:00PM - 10:00PM
Poster Session 3
Room: Bay


Wednesday, January 26 | 8:00PM - 9:00PM
Social Hour
Room: Bay


Thursday, January 27 | 7:00AM - 8:00AM
Breakfast
Room: Granhall


Thursday, January 27 | 8:00AM - 11:15AM
New Strategies for Therapeutic Intervention and Emerging Tec
hnologies that will Help us Sort Out these Issues

Room: Mountain/Lake

Speaker 1 of 7
* Marielle Scherrer-Crosbie, Massachusetts General Hospital, USA

Thursday, January 27 | 8:00AM - 11:15AM
New Strategies for Therapeutic Intervention and Emerging Tec
hnologies that will Help us Sort Out these Issues

Room: Mountain/Lake

Speaker 2 of 7
* Yufang Jin, University of Texas at San Antonio, USA

Thursday, January 27 | 8:00AM - 11:15AM
New Strategies for Therapeutic Intervention and Emerging Tec
hnologies that will Help us Sort Out these Issues

Room: Mountain/Lake

Speaker 3 of 7
Robert G. Gourdie, Virginia Tech Carilion Research Institute, USA
Lessons from Skin Healing for Cardiac Arrhythmia Therapies

Thursday, January 27 | 8:00AM - 11:15AM
New Strategies for Therapeutic Intervention and Emerging Tec
hnologies that will Help us Sort Out these Issues

Room: Mountain/Lake

Speaker 4 of 7
Jennifer E. Van Eyk, Johns Hopkins University, USA
Developing Proteomic Technologies for the Study of Cell Environment Interaction

Thursday, January 27 | 8:00AM - 11:15AM
New Strategies for Therapeutic Intervention and Emerging Tec
hnologies that will Help us Sort Out these Issues

Room: Mountain/Lake

Speaker 5 of 7
David R. Bush, University of Arizona, USA
Short Talk: Quantitation of Pyridinoline and Desmosine Crosslinks from Aorta and Heart by LC/MS/MS

Thursday, January 27 | 8:00AM - 11:15AM
New Strategies for Therapeutic Intervention and Emerging Tec
hnologies that will Help us Sort Out these Issues

Room: Mountain/Lake

Speaker 6 of 7
Merry L. Lindsey, University of Nebraska Medical Center., USA
Using ECM-Specific Microarrays and Proteomics to Gain Insight into Cardiac Remodeling Post-Myocardial Infarction

Thursday, January 27 | 8:00AM - 11:15AM
New Strategies for Therapeutic Intervention and Emerging Tec
hnologies that will Help us Sort Out these Issues

Room: Mountain/Lake

Speaker 7 of 7
Ulrike Mende, Rhode Island Hospital/Brown University, USA
Short Talk: Using a Novel Three-Dimensional Culture Model to Study Heart Cells

Thursday, January 27 | 9:20AM - 9:40AM
Coffee Break
Room: Pre Function


Thursday, January 27 | 11:15AM - 11:15AM
On Own for Lunch and Recreation


Thursday, January 27 | 4:30PM - 5:00PM
Coffee Available
Room: Pre Function


Thursday, January 27 | 5:00PM - 7:00PM
How do Other Organs Regulate ECM in the Heart?
Room: Mountain/Lake
Since the heart is intimately connected to the kidney and brain, these organs play a profound influence on remodeling, as evidenced by angiotensin roles. The role of fluid dynamics as a critical event to dilute ECM components and provide physiological feedback to the vasculature through stretch mechanisms has not been fully investigated.
Speaker 1 of 6
* Robert G. Gourdie, Virginia Tech Carilion Research Institute, USA

Thursday, January 27 | 5:00PM - 7:00PM
How do Other Organs Regulate ECM in the Heart?
Room: Mountain/Lake
Since the heart is intimately connected to the kidney and brain, these organs play a profound influence on remodeling, as evidenced by angiotensin roles. The role of fluid dynamics as a critical event to dilute ECM components and provide physiological feedback to the vasculature through stretch mechanisms has not been fully investigated.
Speaker 2 of 6
* Ulrike Mende, Rhode Island Hospital/Brown University, USA

Thursday, January 27 | 5:00PM - 7:00PM
How do Other Organs Regulate ECM in the Heart?
Room: Mountain/Lake
Since the heart is intimately connected to the kidney and brain, these organs play a profound influence on remodeling, as evidenced by angiotensin roles. The role of fluid dynamics as a critical event to dilute ECM components and provide physiological feedback to the vasculature through stretch mechanisms has not been fully investigated.
Speaker 3 of 6
Harry (Hal) C. Dietz, Johns Hopkins University School of Medicine, Blade Therapeutics, USA
Dissection of a Modifier Network Informs the Pathogenesis and Treatment of Marfan Syndrome

Thursday, January 27 | 5:00PM - 7:00PM
How do Other Organs Regulate ECM in the Heart?
Room: Mountain/Lake
Since the heart is intimately connected to the kidney and brain, these organs play a profound influence on remodeling, as evidenced by angiotensin roles. The role of fluid dynamics as a critical event to dilute ECM components and provide physiological feedback to the vasculature through stretch mechanisms has not been fully investigated.
Speaker 4 of 6
Stephanie Lehoux, McGill University - Jewish General Hospital, Canada
Extracellular Matrix Alterations in Vascular Remodeling

Thursday, January 27 | 5:00PM - 7:00PM
How do Other Organs Regulate ECM in the Heart?
Room: Mountain/Lake
Since the heart is intimately connected to the kidney and brain, these organs play a profound influence on remodeling, as evidenced by angiotensin roles. The role of fluid dynamics as a critical event to dilute ECM components and provide physiological feedback to the vasculature through stretch mechanisms has not been fully investigated.
Speaker 5 of 6
Jan H. N. Lindeman, Leids Universitair Medisch Centre, Netherlands
Short Talk: Distinct Defects in Collagen Micro-Architecture Underlie Vessel Wall Failure in Advanced Abdominal Aneurysms and Aneurysms in Marfan Syndrome

Thursday, January 27 | 5:00PM - 7:00PM
How do Other Organs Regulate ECM in the Heart?
Room: Mountain/Lake
Since the heart is intimately connected to the kidney and brain, these organs play a profound influence on remodeling, as evidenced by angiotensin roles. The role of fluid dynamics as a critical event to dilute ECM components and provide physiological feedback to the vasculature through stretch mechanisms has not been fully investigated.
Speaker 6 of 6
Kenneth Baker, Texas A&M Health Science Center College of Medicine, USA
Intracellular Renin-Angiotensin System: Implications on ECM in Diabetic Models

Thursday, January 27 | 7:00PM - 7:15PM
Concluding Remarks
Room: Mountain/Lake

Speaker 1 of 2
* Merry L. Lindsey, University of Nebraska Medical Center., USA

Thursday, January 27 | 7:00PM - 7:15PM
Concluding Remarks
Room: Mountain/Lake

Speaker 2 of 2
* Thomas K. Borg, Medical University of South Carolina, USA

Thursday, January 27 | 7:15PM - 8:15PM
Social Hour
Room: Alumni


Thursday, January 27 | 8:00PM - 9:00PM
Dinner
Room: Granhall


Thursday, January 27 | 8:00PM - 11:00PM
Entertainment
Room: Granhall


Friday, January 28 | 10:25AM - 10:25AM
Departure


*Session Chair.