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The patterns of molecular and biochemical ECM alterations in failing hearts are dependent on the type of underlying injury. Pressure overload triggers early activation of a matrix-synthetic program in cardiac fibroblasts, inducing myofibroblast conversion, and stimulating synthesis of both structural and matricellular ECM proteins. Expansion of the cardiac ECM may increase myocardial stiffness promoting diastolic dysfunction. Cardiomyocytes, vascular cells and immune cells, activated through mechanosensitive pathways or neurohumoral mediators may play a critical role in fibroblast activation through secretion of cytokines and growth factors. Sustained pressure overload leads to dilative remodeling and systolic dysfunction that may be mediated by changes in the interstitial protease\/antiprotease balance. On the other hand, ischemic injury causes dynamic changes in the cardiac ECM that contribute to regulation of inflammation and repair and may mediate adverse cardiac remodeling. In other pathophysiologic conditions, such as volume overload, diabetes mellitus, and obesity, the cell biological effectors mediating ECM remodeling are poorly understood and the molecular links between the primary insult and the changes in the matrix environment are unknown. This review article discusses the role of ECM macromolecules in heart failure, focusing on both structural ECM proteins (such as fibrillar and nonfibrillar collagens), and specialized injury-associated matrix macromolecules (such as fibronectin and matricellular proteins). Understanding the role of the ECM in heart failure may identify therapeutic targets to reduce geometric remodeling, to attenuate cardiomyocyte dysfunction, and even to promote myocardial regeneration.<\/jats:p>","DOI":"10.1161\/circresaha.119.311148","type":"journal-article","created":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T14:00:28Z","timestamp":1561039228000},"page":"117-146","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":499,"title":["The Extracellular Matrix in Ischemic and Nonischemic Heart Failure"],"prefix":"10.1161","volume":"125","author":[{"given":"Nikolaos G.","family":"Frangogiannis","sequence":"first","affiliation":[{"name":"From the Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology), Albert Einstein College of Medicine, Bronx, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3904"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176009"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.11.001"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-014-0992-x"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/17.1.15"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1431927611012438"},{"key":"e_1_3_4_8_2","first-page":"2037","article-title":"The collagen matrix of the heart.","volume":"40","author":"Borg TK","year":"1981","unstructured":"Borg, TK, Caulfield, JB. 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