1002-98 Platelet-derived growth factor signaling has a crucial role in vascular maturation following myocardial infarction

Zymek, Paweł; Nasser, Kamal; Tincey, Sophia; Ren, Guofeng; Dobaczewski, Marcin; Michael, Lloyd H.; Entman, Mark L.; Frangogiannis, Nikolaos G.

doi:10.1016/s0735-1097(04)91041-8

Cited by 1 publication

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“…In addition to its critical effects on myofibroblast conversion, TGF-β also activates a matrix-preserving program in cardiac fibroblasts through Smad-dependent signaling 218, 234 . Other fibrogenic mediators, such as thePDGFs 235, 236 , members of the fibroblast growth factor (FGF) family, 237 and the mast cell-derived proteases tryptase 238 and chymase 239 are also released in the infarcted heart and may activate infarct myofibroblasts.…”

Section: The Reparative and Proliferative Phasementioning

confidence: 99%

The Biological Basis for Cardiac Repair After Myocardial Infarction

Prabhu

Frangogiannis

2016

Circulation Research

1,651

1,396

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In adult mammals, massive sudden loss of cardiomyocytes following infarction overwhelms the limited regenerative capacity of the myocardium, resulting in formation of a collagen-based scar. Necrotic cells release danger signals, activating innate immune pathways and triggering an intense inflammatory response. Stimulation of toll-like receptor signaling and complement activation induces expression of pro-inflammatory cytokines (such as interleukin-1 and tumor necrosis factor-α) and chemokines (such as monocyte chemoattractant protein-1/CCL2). Inflammatory signals promote adhesive interactions between leukocytes and endothelial cells, leading to extravasation of neutrophils and monocytes. As infiltrating leukocytes clear the infarct from dead cells, mediators repressing inflammation are released, and anti-inflammatory mononuclear cell subsets predominate. Suppression of the inflammatory response is associated with activation of reparative cells. Fibroblasts proliferate, undergo myofibroblast transdifferentiation, and deposit large amounts of extracellular matrix proteins maintaining the structural integrity of the infarcted ventricle. The renin-angiotensin-aldosterone system and members of the transforming growth factor-β family play an important role in activation of infarct myofibroblasts. Maturation of the scar follows, as a network of cross-linked collagenous matrix is formed and granulation tissue cells become apoptotic. This review discusses the cellular effectors and molecular signals regulating the inflammatory and reparative response following myocardial infarction. Dysregulation of immune pathways, impaired suppression of post-infarction inflammation, perturbed spatial containment of the inflammatory response, and overactive fibrosis may cause adverse remodeling in patients with infarction contributing to the pathogenesis of heart failure. Therapeutic modulation of the inflammatory and reparative response may hold promise for prevention of post-infarction heart failure.

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