The extracellular matrix in myocardial injury, repair, and remodeling
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TLDR
The role of the ECM in cardiac repair and remodeling is reviewed and matrix-based therapies that may attenuate remodeling while promoting repair and regeneration are discussed.Abstract:
The cardiac extracellular matrix (ECM) not only provides mechanical support, but also transduces essential molecular signals in health and disease. Following myocardial infarction, dynamic ECM changes drive inflammation and repair. Early generation of bioactive matrix fragments activates proinflammatory signaling. The formation of a highly plastic provisional matrix facilitates leukocyte infiltration and activates infarct myofibroblasts. Deposition of matricellular proteins modulates growth factor signaling and contributes to the spatial and temporal regulation of the reparative response. Mechanical stress due to pressure and volume overload and metabolic dysfunction also induce profound changes in ECM composition that contribute to the pathogenesis of heart failure. This manuscript reviews the role of the ECM in cardiac repair and remodeling and discusses matrix-based therapies that may attenuate remodeling while promoting repair and regeneration.read more
Citations
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Cardiac fibrosis: Cell biological mechanisms, molecular pathways and therapeutic opportunities.
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Specialized fibroblast differentiated states underlie scar formation in the infarcted mouse heart
Xing Fu,Xing Fu,Hadi Khalil,Onur Kanisicak,Justin G. Boyer,Ronald J. Vagnozzi,Bryan D. Maliken,Michelle A. Sargent,Vikram Prasad,Iñigo Valiente-Alandi,Burns C. Blaxall,Jeffery D. Molkentin,Jeffery D. Molkentin +12 more
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The Extracellular Matrix in Ischemic and Nonischemic Heart Failure.
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Extracellular matrix remodeling and cardiac fibrosis.
TL;DR: Understanding the comprehensive molecules and pathways involved in ECM homeostasis and remodeling may provide important novel potential targets for preventing and treating cardiac fibrosis.
References
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Extracellular matrix remodeling in canine and mouse myocardial infarcts
Marcin Dobaczewski,Marcin Bujak,Pawel Zymek,Guofeng Ren,Mark L. Entman,Nikolaos G. Frangogiannis +5 more
TL;DR: Deposition of the provisional matrix was more transient in the mouse infarct and was followed by earlier formation of a mature collagen-based scar after 7–14 days of reperfusion, while that in the canineinfarct was highly cellular and evolving.
Journal ArticleDOI
P2Y6 receptor-Gα12/13 signalling in cardiomyocytes triggers pressure overload-induced cardiac fibrosis
Motohiro Nishida,Yoji Sato,Aya Uemura,Yusuke Narita,Hidetoshi Tozaki-Saitoh,Michio Nakaya,Tomomi Ide,Kazuhiro Suzuki,Kazuhide Inoue,Taku Nagao,Hitoshi Kurose +10 more
TL;DR: Results indicate that activation of Gα12/13 in cardiomyocytes by the extracellular nucleotides‐stimulated P2Y6 receptor triggers fibrosis in pressure overload‐induced cardiac fibrosis, which works as an upstream mediator of the signalling pathway between Ang II and TGF‐β.
Journal ArticleDOI
Novel Function of Alternatively Activated Macrophages: Stabilin-1-Mediated Clearance of SPARC
Julia Kzhyshkowska,Gail Workman,Marina Cardó-Vila,Wadih Arap,Renata Pasqualini,Alexei Gratchev,Liis Krusell,Sergij Goerdt,E. Helene Sage +8 more
TL;DR: It is proposed that alternatively activated macrophages coordinate extracellular matrix remodeling, angiogenesis, and tumor progression via stabilin-1-mediated endocytosis of SPARC and thereby regulate itsextracellular concentration.
Journal ArticleDOI
CD44 Is Critically Involved in Infarct Healing by Regulating the Inflammatory and Fibrotic Response
Peter Huebener,Tareq Abou-Khamis,Pawel Zymek,Marcin Bujak,Xia Ying,Khaled Chatila,Sandra B. Haudek,Geeta D. Thakker,Nikolaos G. Frangogiannis +8 more
TL;DR: The findings suggest that CD44-mediated interactions are critically involved in infarct healing, and CD44 signaling is important for resolution of the postinfarction inflammatory reaction and regulates fibroblast function.
Journal ArticleDOI
MMP generated matrikines.
TL;DR: The role of matrix metalloproteinases (MMPs) in the generation of matrikines has been discussed in this paper, where a review highlights the roles of MMPs in generating these important matrikine fragments.