Journal of Molecular and Cellular Cardiology RSS feed: Current Issue. The Journal of Molecular and Cellular Cardiology publishes work advancing knowledge of the mechanisms responsible for both normal and diseased cardiovascular function. To this end papers are published in all relevant areas. These include (but are not limited to): structural biology; genetics; proteomics; morphology; stem cells; molecular biology; metabolism; biophysics; electrophysiology; pharmacology and physiology. Papers are encouraged with both basic and translational approaches. The journal is directed not only to basic scientists but also to clinical cardiologists who wish to follow the rapidly advancing frontiers of basic knowledge of the heart and circulation. JMCC Early Career Author's Prize The incoming Editor-in-Chief, David Eisner, and Roberto Bolli, President of the ISHR, are pleased to make the following announcement: We are delighted to announce a new prize designed to recognize outstanding papers published by early career authors in the Journal of Molecular and Cellular Cardiology. The first prize (sponsored jointly by ISHR and the publishers, Elsevier) will comprise $750. Two runners up will receive commendations and $250 each. The winners will be announced in the JMCC. Entries for the JMCC Young Authors Prize are invited from early career scientists who are either the first or last author of a paper published in JMCC in a given year. Applicants must have received their research degree (MD, PhD or equivalent) less than 6 years before submitting the paper. In the case of candidates who have both a MD and PhD the date of the most recently awarded degree is the relevant one. US National Institutes of Health (NIH) voluntary posting ("Public Access") policy Journal of Molecular and Cellular Cardiology and Elsevier facilitate the author's response to the NIH Public Access Policy. For more details please see the Guide for authors http://www.jmmc-online.com/?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. All rights reserved. Journal of Molecular and Cellular Cardiology0022-2828483March 2010 © 2010 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.jmmc-online.com/article/PIIS0022282810000179/abstract?rss=yesEditorial Board10.1016/S0022-2828(10)00017-9Journal of Molecular and Cellular Cardiology 48, 3 (2010)2010-03-01Journal of Molecular and Cellular Cardiology2010-03-01483S0022-2828(10)X0002-5iihttp://www.jmmc-online.com/article/PIIS0022282809003836/abstract?rss=yesFor many years, analyses of the heart have focused primarily on the role of the myocytes as the principal cell type that generates force. Analyses of the extracellular matrix (ECM) were deemed important, but primarily relevant only in hypertrophy and after myocardial infarction. Related to the ECM was the role of the fibroblast, the principal cell type that makes the ECM. When analyses of the ECM were performed, the focus was primarily on interstitial collagen. This reductionist approach was also incorporated into the experimental design of in vitro studies that used planar two-dimensional culture systems.Understanding the role of the extracellular matrix in cardiovascular development and disease: Where do we go from here?Merry L. Lindsey, Thomas K. Borg10.1016/j.yjmcc.2009.09.007Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-09-24Journal of Molecular and Cellular Cardiology2009-09-24483S0022-2828(10)X0002-5Editorial431432http://www.jmmc-online.com/article/PIIS002228280900426X/abstract?rss=yesAbstract: Vascular cells are very sensitive to their hemodynamic environment. Any change in blood pressure or blood flow can be sensed by endothelial and vascular smooth muscle cells and ultimately results in structural modifications within the vascular wall that accommodate the new conditions. In the case of hypertension, the increase in arterial stretch stimulates vessel thickening to normalize the tensile forces. This process requires modification of the extracellular matrix and of cell–matrix interactions, which mainly involves extracellular proteases. In hypertension, chronic exposure of the arterial wall to stretch leads to vascular remodeling, arterial stiffness and calcification, which finally affect target organ function. This review surveys how mechanical stretch regulates extracellular proteases, considering the signaling pathways involved and the consequences on the cardiovascular system.Extracellular matrix alterations in hypertensive vascular remodelingCatherine A. Lemarié, Pierre-Louis Tharaux, Stéphanie Lehoux10.1016/j.yjmcc.2009.09.018Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-10-19Journal of Molecular and Cellular Cardiology2009-10-19483S0022-2828(10)X0002-5Reviews433439http://www.jmmc-online.com/article/PIIS0022282809004167/abstract?rss=yesAbstract: Matrix metalloproteinases (MMPs) are a group of proteases known to regulate the turnover of extracellular matrix and thus are suggested to be important in the process of several diseases associated with tissue remodeling. Furthermore, the concept that modulation of airway remodeling including excessive proteolysis damage of the tissue, may be of interest as a basis for future treatment. Degradation of extracellular matrix is currently associated with structural and recruited cell activation and release of inflammatory mediators and MMPs. Indeed, a marked increase in their expression is observed associated with a variety of inflammatory diseases, including respiratory pathologies. In these conditions, we have to consider MMPs as therapeutic targets which can be inhibited by non-selective and/or selective inhibitors as anti-inflammatory compounds. The present review aims to discuss the potential interest of the inhibition of MMP in inflammatory diseases with a focus on respiratory diseases.Role of matrix metalloproteinases in the inflammatory process of respiratory diseasesVincent Lagente, Elisabeth Boichot10.1016/j.yjmcc.2009.09.017Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-10-09Journal of Molecular and Cellular Cardiology2009-10-09483S0022-2828(10)X0002-5Reviews440444http://www.jmmc-online.com/article/PIIS002228280900412X/abstract?rss=yesAbstract: Unraveling the biological role of tissue inhibitors of metalloproteinases (TIMPs) during cardiac remodeling and the progression of heart failure has proven to be an enormous challenge. Remodeling of the cardiac extracellular matrix (ECM), regulated by matrix metalloproteinases (MMPs) and their endogenous inhibitors, TIMPs, is a well-established paradigm in cardiac health and disease. Originally, TIMPs were thought to function exclusively as endogenous inhibitors of MMP activity, thereby fine-tuning MMP-mediated ECM degradation and numerous related processes. However, during the last two decades, the concept of MMP-independent TIMP-mediated receptor signaling and regulation of cell fate has emerged. Although our current knowledge is still limited, in this review, we highlight some of the novel data, illustrating the MMP-independent biological properties of the four TIMP family members. Moreover, we discuss how these cell-specific insights may contribute to the process of cardiac remodeling, disease and failure. Finally, we identify where additional research is needed that will codetermine the possible future of TIMPs as therapeutic targets.TIMPs and cardiac remodeling: ‘Embracing the MMP-independent-side of the family’Davy Vanhoutte, Stephane Heymans10.1016/j.yjmcc.2009.09.013Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-10-05Journal of Molecular and Cellular Cardiology2009-10-05483S0022-2828(10)X0002-5Reviews445453http://www.jmmc-online.com/article/PIIS0022282809003782/abstract?rss=yesAbstract: This review addresses new concepts related to the importance of how cells within the cardiovascular system respond to matricryptic sites generated from the extracellular matrix (ECM) following tissue injury. A model is presented whereby matricryptic sites exposed from the ECM result in activation of multiple cell surface receptors including integrins, scavenger receptors, and toll-like receptors which together are hypothesized to coactivate downstream signaling pathways which alter cell behaviors following tissue injury. Of great interest are the relationships between matricryptic fragments of ECM called matricryptins and other stimuli that activate cells during injury states such as released components from cells (DNA, RNA, cytoskeletal components such as actin) or products from infectious agents in innate immunity responses. These types of cell activating molecules, which are composed of repeating molecular elements, are known to interact with pattern recognition receptors that (i) are expressed from cell surfaces, (ii) are released from cells following tissue injury, or (iii) circulate as components of plasma. Thus, cell recognition of matricryptic sites from the ECM appears to be an important component of a broad cell and tissue sensory system to detect and respond to environmental cues generated following varied types of tissue injury.Matricryptic sites control tissue injury responses in the cardiovascular system: Relationships to pattern recognition receptor regulated eventsGeorge E. Davis10.1016/j.yjmcc.2009.09.002Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-09-14Journal of Molecular and Cellular Cardiology2009-09-14483S0022-2828(10)X0002-5Reviews454460http://www.jmmc-online.com/article/PIIS0022282809003770/abstract?rss=yesAbstract: Atrial fibrosis has been strongly associated with the presence of heart diseases/arrhythmias, including congestive heart failure (CHF) and atrial fibrillation (AF). Inducibility of AF as a result of atrial fibrosis has been the subject of intense recent investigation since it is the most commonly encountered arrhythmia in adults and can substantially increase the risk of premature death. Rhythm and rate control drugs as well as surgical interventions are used as therapies for AF; however, increased attention has been diverted to mineralocorticoid receptor (MR) antagonists including spironolactone as potential therapies for human AF because of their positive effects on reducing atrial fibrosis and associated AF in animal models. Spironolactone has been shown to exert positive effects in human patients with heart failure; however, the mechanisms and effects in human atrial fibrosis and AF remain undetermined. This review will discuss and highlight developments on (i) the relationship between atrial fibrosis and AF, (ii) spironolactone, as a drug targeted to atrial fibrosis and AF, as well as (iii) the distinct and common mechanisms important for regulating atrial and ventricular fibrosis, inclusive of the key extracellular matrix regulatory proteins involved.Extracellular matrix remodeling in atrial fibrosis: Mechanisms and implications in atrial fibrillationJason Pellman, Robert C. Lyon, Farah Sheikh10.1016/j.yjmcc.2009.09.001Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-09-14Journal of Molecular and Cellular Cardiology2009-09-14483S0022-2828(10)X0002-5Reviews461467http://www.jmmc-online.com/article/PIIS0022282809003666/abstract?rss=yesAbstract: Myocarditis is an inflammatory disorder induced most commonly by infectious agents. The natural course of the disease is broad and ranges from complete recovery to dilated cardiomyopathy and death. The mechanisms of the incomplete recovery remain poorly understood but extracellular matrix remodelling by metalloproteinases seems to be important for the progression to dilated cardiomyopathy and chronic heart failure. The matrix metalloproteinases (MMPs) are proteolytic enzymes whose role was thought to be the degradation of matrix components only. In the last few years a considerable amount of evidence has gathered which shows new functions of the MMPs as powerful modulatory factors in inflammatory disorders. MMPs facilitate the migration of immune cells through the basement membrane, process cytokines and chemokines by modulating their function, and regulate the relationship of cells with ECM components. These findings enhance our knowledge of the role of MMPs in viral myocarditis and inflammatory cardiomyopathy and may lead to a new understanding which might allow for specific and successful therapeutic interventions in the future.Immunomodulation and matrix metalloproteinases in viral myocarditisDirk Westermann, Konstantinos Savvatis, Heinz-Peter Schultheiss, Carsten Tschöpe10.1016/j.yjmcc.2009.08.019Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-09-02Journal of Molecular and Cellular Cardiology2009-09-02483S0022-2828(10)X0002-5Reviews468473http://www.jmmc-online.com/article/PIIS0022282809003605/abstract?rss=yesAbstract: The extracellular matrix is not only a scaffold that provides support for cells, but it is also involved in cell–cell interactions, proliferation and migration. The intricate relationships among the cellular and acellular components of the heart drive proper heart development, homeostasis and recovery following pathological injury. Cardiac myocytes, fibroblasts and endothelial cells differentially express and respond to particular extracellular matrix factors that contribute to cell communication and overall cardiac function. In addition, turnover and synthesis of ECM components play an important role in cardiac function. Therefore, a better understanding of these factors and their regulation would lend insight into cardiac development and pathology, and would open doors to novel targeted pharmacologic therapies. This review highlights the importance of contributions of particular cardiac cell populations and extracellular matrix factors that are critical to the development and regulation of heart function.The extracellular matrix: At the center of it allStephanie L.K. Bowers, Indroneal Banerjee, Troy A. Baudino10.1016/j.yjmcc.2009.08.024Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-09-02Journal of Molecular and Cellular Cardiology2009-09-02483S0022-2828(10)X0002-5Reviews474482http://www.jmmc-online.com/article/PIIS0022282809003265/abstract?rss=yesAbstract: The circulating renin-angiotensin system (RAS) is a classic endocrine system that regulates cardiovascular homeostasis during physiologic and pathologic states. Accumulated evidence has shown the presence of components of RAS in various tissues, which are upregulated in certain pathological conditions. Locally produced angiotensin (Ang)II may play an important role in tissue repair/remodeling in autocrine and/or paracrine manners. Following acute myocardial infarction (MI), cardiac repair occurs in the infarcted myocardium and structural remodeling is developed in noninfarcted myocardium, which are accompanied by activated cardiac RAS. In this review, the current understanding of independent activation of cardiac RAS and its regulation in the pathogenesis of myocardial repair/remodeling after MI is discussed.Intracardiac renin–angiotensin system and myocardial repair/remodeling following infarctionYao Sun10.1016/j.yjmcc.2009.08.002Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-08-13Journal of Molecular and Cellular Cardiology2009-08-13483S0022-2828(10)X0002-5Reviews483489http://www.jmmc-online.com/article/PIIS0022282809003253/abstract?rss=yesAbstract: Extracellular matrix (ECM) components play essential roles in development, remodeling, and signaling in the cardiovascular system. They are also important in determining the mechanics of blood vessels, valves, pericardium, and myocardium. The goal of this brief review is to summarize available information regarding the mechanical contributions of ECM in the myocardium. Fibrillar collagen, elastin, and proteoglycans all play crucial mechanical roles in many tissues in the body generally and in the cardiovascular system specifically. The myocardium contains all three components, but their mechanical contributions are relatively poorly understood. Most studies of ECM contributions to myocardial mechanics have focused on collagen, but quantitative prediction of mechanical properties of the myocardium, or changes in those properties with disease, from measured tissue structure is not yet possible. Circumstantial evidence suggests that the mechanics of cardiac elastin and proteoglycans merit further study. Work in other tissues used a combination of correlation, modification or digestion, and mathematical modeling to establish mechanical roles for specific ECM components; this work can provide guidance for new experiments and modeling studies in myocardium.Contribution of extracellular matrix to the mechanical properties of the heartGregory M. Fomovsky, Stavros Thomopoulos, Jeffrey W. Holmes10.1016/j.yjmcc.2009.08.003Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-08-17Journal of Molecular and Cellular Cardiology2009-08-17483S0022-2828(10)X0002-5Reviews490496http://www.jmmc-online.com/article/PIIS0022282809003149/abstract?rss=yesAbstract: The remodeling of a heart ventricle after myocardial infarction involves numerous inflammatory mediators that may trigger a long-lasting and a highly fibrogenic process. Likewise, in the kidney, acute and chronic injuries may lead to abnormal extracellular matrix deposition and eventually lead to the loss of renal function. Major breakthroughs have emerged during the last ten years with respect to the pathophysiology of matrix remodeling. Epithelial and endothelial cells are plastic, and able to engage in epithelial (or endothelial)-to-mesenchymal transition (EMT or EndMT), thus actively contributing to the fibrogenesis. Members of the fibrinolytic system were demonstrated to possess unsuspected properties and interact with receptors and integrins on endothelial and epithelial cells. Finally, a notion that stem cells could integrate into damaged tissue has recently emerged, which likely contributes to the tissue repair. In many aspects, the kidney and the heart share many common injury mechanisms. We envision that some of them will be accessible as common therapeutic targets in the future.Renal studies provide an insight into cardiac extracellular matrix remodeling during health and diseaseAlexandre Hertig, Taduri Gangadhar, Raghu Kalluri10.1016/j.yjmcc.2009.07.022Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-07-31Journal of Molecular and Cellular Cardiology2009-07-31483S0022-2828(10)X0002-5Reviews497503http://www.jmmc-online.com/article/PIIS0022282809003083/abstract?rss=yesAbstract: The dynamic alterations in the cardiac extracellular matrix following myocardial infarction not only determine the mechanical properties of the infarcted heart, but also directly modulate the inflammatory and reparative response. During the inflammatory phase of healing, rapid activation of Matrix Metalloproteinases (MMP) causes degradation of the cardiac extracellular matrix. Matrix fragments exert potent pro-inflammatory actions, while MMPs process cytokines and chemokines altering their biological activity. In addition, vascular hyperpermeability results in extravasation of fibronectin and fibrinogen leading to formation of a plasma-derived provisional matrix that serves as a scaffold for leukocyte infiltration. Clearance of the infarct from dead cells and matrix debris is essential for resolution of inflammation and marks the transition to the proliferative phase. The fibrin-based provisional matrix is lysed and cellular fibronectin is secreted. ED-A fibronectin, mechanical tension and Transforming Growth Factor (TGF)-β are essential for modulation of fibroblasts into myofibroblasts, the main collagen-secreting cells in the wound. The matricellular proteins thrombospondin-1 and -2, osteopontin, tenascin-C, periostin, and secreted protein acidic and rich in cysteine (SPARC) are induced in the infarct regulating cellular interactions and promoting matrix organization. As the infarct matures, matrix cross-linking results in formation of a dense collagen-based scar. At this stage, shielding of fibroblasts from external mechanical tension by the mature matrix network may promote deactivation and cellular quiescence. The components of the extracellular matrix do not passively follow the pathologic alterations of the infarcted heart but critically modulate inflammatory and reparative pathways by transducing signals that affect cell survival, phenotype and gene expression.The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarctionMarcin Dobaczewski, Carlos Gonzalez-Quesada, Nikolaos G. Frangogiannis10.1016/j.yjmcc.2009.07.015Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-07-24Journal of Molecular and Cellular Cardiology2009-07-24483S0022-2828(10)X0002-5Reviews504511http://www.jmmc-online.com/article/PIIS0022282809002788/abstract?rss=yesAbstract: Extracellular matrix disturbances play an important role in the development of ventricular remodeling and failure. Genetically modified mice with abnormalities in the synthesis and degradation of extracellular matrix have been generated, in particular mice with deletion or overexpression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). Echocardiography is ideally suited to serially evaluate left ventricular (LV) size and function, thus defining the progression of LV remodeling and failure. This Review describes the echocardiographic parameters that may provide insights into the development of ventricular remodeling and heart failure. The application of echocardiography to study LV remodeling and function after myocardial infarction and LV pressure-overload in wild-type mice and mice deficient or overexpressing MMPs or TIMPs is then detailed. Finally, using the example of mice deficient in nitric oxide synthase 3, a cautionary example is given illustrating discrepancies between the cardiac echocardiographic phenotype and modifications of the extracellular matrix.Ventricular remodeling and function: Insights using murine echocardiographyMarielle Scherrer-Crosbie, Baptiste Kurtz10.1016/j.yjmcc.2009.07.004Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-07-16Journal of Molecular and Cellular Cardiology2009-07-16483S0022-2828(10)X0002-5Reviews512517http://www.jmmc-online.com/article/PIIS0022282809002739/abstract?rss=yesAbstract: The review describes the role of loose connective tissues with focus on transcapillary exchange and edema formation with relevance for inflammation, fibrosis and tumors. Based on studies in these tissues, comparisons are made to the fibrotic processes in the heart.Edema and fluid dynamics in connective tissue remodellingRolf K. Reed, Åsa Lidén, Kristofer Rubin10.1016/j.yjmcc.2009.06.023Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-07-13Journal of Molecular and Cellular Cardiology2009-07-13483S0022-2828(10)X0002-5Reviews518523http://www.jmmc-online.com/article/PIIS0022282809002715/abstract?rss=yesAbstract: In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies are termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies is imperative. Currently, there is no single diagnostic method for the identification of diabetic cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition. Early changes in cardiac function are typically manifested as abnormal diastolic function that with time leads to loss of contractile function. Echocardiography based methods currently stand as the preferred diagnostic approach for diabetic cardiomyopathy, due to its wide availability and economical use. In addition to conventional techniques, magnetic resonance imaging and spectroscopy along with contrast agents are now leading new approaches in the diagnosis of myocardial fibrosis, and cardiac and hepatic metabolic changes. These strategies can be complemented with serum biomarkers so they can offer a clear picture as to diabetes-induced changes in cardiac structure/function even at very early stages of the disease. This review article intends to provide a summary of experimental and routine tools currently available to diagnose diabetic cardiomyopathy induced changes in cardiac structure/function. These tools can be reliably used in either experimental models of diabetes or for clinical applications.Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosisLisandro Maya, Francisco J. Villarreal10.1016/j.yjmcc.2009.06.021Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-07-13Journal of Molecular and Cellular Cardiology2009-07-13483S0022-2828(10)X0002-5Reviews524529http://www.jmmc-online.com/article/PIIS0022282809002685/abstract?rss=yesAbstract: Cardiac remodeling is accelerated during pathological conditions and several anabolic and catabolic regulators work in concert to repair the myocardium and maintain its functionality. The fibroblasts play a major role in this process via collagen deposition as well as supplying the degradative matrix metalloproteinases. During the more acute responses to a myocardial infarction (MI) the heart relies on a more aggressive wound healing sequence that includes the myofibroblasts, specialized secretory cells necessary for infarct scar formation and thus, rescue of the myocardium. The activated fibroblasts and myofibroblasts deposit large amounts of fibrillar collagen during the post-MI wound healing phase, type I and III collagen are the most abundant collagens in the heart and they maintain the structural integrity under normal and disease states. While collagen I and III have been the traditional focus of the myocardial matrix, recent studies have suggested that the non-fibrillar collagens (types IV and VI) are also deposited during pathological wound healing and may play key roles in myofibroblast differentiation and organization of the fibrillar collagen network. This review highlights the potential roles of the non-fibrillar collagens and how they work in concert with the fibrillar collagens in mediating myocardial remodeling.Non-fibrillar collagens: Key mediators of post-infarction cardiac remodeling?Patricia E. Shamhart, J. Gary Meszaros10.1016/j.yjmcc.2009.06.017Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-07-01Journal of Molecular and Cellular Cardiology2009-07-01483S0022-2828(10)X0002-5Reviews530537http://www.jmmc-online.com/article/PIIS0022282809002661/abstract?rss=yesAbstract: Remodeling after myocardial infarction (MI) associates with left ventricular (LV) dilation, decreased cardiac function and increased mortality. The dynamic synthesis and breakdown of extracellular matrix (ECM) proteins play a significant role in myocardial remodeling post-MI. Expression of osteopontin (OPN) increases in the heart post-MI. Evidence has been provided that lack of OPN induces LV dilation which associates with decreased collagen synthesis and deposition. Inhibition of matrix metalloproteinases, key players in ECM remodeling process post-MI, increased ECM deposition (fibrosis) and improved LV function in mice lacking OPN after MI. This review summarizes — 1) signaling pathways leading to increased expression of OPN in the heart; 2) the alterations in the structure and function of the heart post-MI in mice lacking OPN; and 3) mechanisms involved in OPN-mediated ECM remodeling post-MI.Osteopontin: Role in extracellular matrix deposition and myocardial remodeling post-MIMahipal Singh, Cerrone R. Foster, Suman Dalal, Krishna Singh10.1016/j.yjmcc.2009.06.015Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-07-01Journal of Molecular and Cellular Cardiology2009-07-01483S0022-2828(10)X0002-5Reviews538543http://www.jmmc-online.com/article/PIIS002228280900265X/abstract?rss=yesAbstract: The cardiac interstitium is a unique and adaptable extracellular matrix (ECM) that provides a milieu in which myocytes, fibroblasts, and endothelial cells communicate and function. The composition of the ECM in the heart includes structural proteins such as fibrillar collagens and matricellular proteins that modulate cell:ECM interaction. Secreted Protein Acidic and Rich in Cysteine (SPARC), a collagen-binding matricellular protein, serves a key role in collagen assembly into the ECM. Recent results demonstrated increased cardiac rupture, dysfunction and mortality in SPARC-null mice in response to myocardial infarction that was associated with a decreased capacity to generate organized, mature collagen fibers. In response to pressure overload induced-hypertrophy, the decrease in insoluble collagen incorporation in the left ventricle of SPARC-null hearts was coincident with diminished ventricular stiffness in comparison to WT mice with pressure overload. This review will focus on the role of SPARC in the regulation of interstitial collagen during cardiac remodeling following myocardial infarction and pressure overload with a discussion of potential cellular mechanisms that control SPARC-dependent collagen assembly in the heart.Cardiac extracellular matrix remodeling: Fibrillar collagens and Secreted Protein Acidic and Rich in Cysteine (SPARC)Sarah McCurdy, Catalin F. Baicu, Stephane Heymans, Amy D. Bradshaw10.1016/j.yjmcc.2009.06.018Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-07-06Journal of Molecular and Cellular Cardiology2009-07-06483S0022-2828(10)X0002-5Reviews544549http://www.jmmc-online.com/article/PIIS0022282809002636/abstract?rss=yesAbstract: Regenerative healing is the process by which injured tissues are restored to their original structure and function. Many species are capable of healing in this manner. However, in mammals the healing response in most tissues is marked by fibroblast proliferation and scar tissue deposition. While scarring contributes to efficient resolution of mammalian wounds and restoration of at least partial structural and functional support, the final result of scar formation can be more deleterious than the initial insult. This is especially true in the heart, which is sensitive to electrical heterogeneities and altered mechanical properties produced by scarring. Several therapeutic modalities promoting regeneration in skin wounds have been developed that modulate various aspects of the healing process. Targets include cytokine stimulation, control of fibroblast activation, modulation of gap junctions, and stem cell differentiation. Here, we review and compare mechanisms of injury, repair, and scarring in the skin and heart and discuss the promise and caveats of future therapies that may translate to improving repair of myocardial tissues.Translational lessons from scarless healing of cutaneous wounds and regenerative repair of the myocardiumJoseph A. Palatinus, J. Matthew Rhett, Robert G. Gourdie10.1016/j.yjmcc.2009.06.013Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-06-29Journal of Molecular and Cellular Cardiology2009-06-29483S0022-2828(10)X0002-5Reviews550557http://www.jmmc-online.com/article/PIIS0022282809002600/abstract?rss=yesAbstract: The concept that extracellular matrix (ECM) turnover occurs during cardiac remodeling is a well-accepted paradigm. To date, a multitude of studies document that remodeling is accompanied by increases in the synthesis and deposition of ECM components as well as increases in extracellular proteases, especially matrix metalloproteinases (MMPs), which break down ECM components. Further, soluble ECM fragments generated from enzymatic action serve to stimulate cell behavior and have been proposed as candidate plasma biomarkers of cardiac remodeling. This review briefly summarizes our current knowledge base on cardiac ECM turnover following myocardial infarction (MI), but more importantly extends discussion by defining avenues that remain to be explored to drive the ECM remodeling field forward. Specifically, this review will discuss cause and effect roles for the ECM changes observed following MI and the potential role of the ECM changes that may serve as trigger points to regulate remodeling. While the pattern of remodeling following MI is qualititatively similar but quantitively different from various types of injury, the basic theme in remodeling is repeated. Therefore, while we use the MI model as the prototype injury model, the themes discussed here are also relevant to cardiac remodeling due to other types of injury.Extracellular matrix turnover and signaling during cardiac remodeling following MI: Causes and consequencesRogelio Zamilpa, Merry L. Lindsey10.1016/j.yjmcc.2009.06.012Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-06-26Journal of Molecular and Cellular Cardiology2009-06-26483S0022-2828(10)X0002-5Reviews558563http://www.jmmc-online.com/article/PIIS0022282809002296/abstract?rss=yesAbstract: Volume overload-induced heart failure results in progressive left ventricular remodeling characterized by chamber dilation, eccentric cardiac myocyte hypertrophy and changes in extracellular matrix (ECM) remodeling changes. The ECM matrix scaffold is an important determinant of the structural integrity of the myocardium and actively participates in force transmission across the LV wall. In response to this hemodynamic overload, the ECM undergoes a distinct pattern of remodeling that differs from pressure overload. Once thought to be a static entity, the ECM is now regarded to be a highly adaptive structure that is dynamically regulated by mechanical stress, neurohormonal activation, inflammation and oxidative stress, that result in alterations in collagen and other matrix components and a net change in matrix metalloproteinase (MMP) expression and activation. These changes dictate overall ECM turnover during volume overload hear failure progression. This review will discuss the cellular and molecular mechanisms that dictate the temporal patterns of ECM remodeling during heart disease progression.Extracellular matrix remodeling during the progression of volume overload-induced heart failureKirk R. Hutchinson, James A. Stewart, Pamela A. Lucchesi10.1016/j.yjmcc.2009.06.001Journal of Molecular and Cellular Cardiology 48, 3 (2010)2009-06-15Journal of Molecular and Cellular Cardiology2009-06-15483S0022-2828(10)X0002-5Reviews564569