Cardiac pericytes mediate the remodeling response to myocardial infarction

Cardiac Pericyte Diversity in Infarct Remodeling: Not Just Vascular Support Cells?

“…A recent study using Cspg4 and Tbx18 reporter and inducible Cre lines also described activation of a fibrogenic program in pericytes after MI. 14 However, contrary to Alex et al 11 , disruption of TGF-β signaling in pericytes and their derivatives did not affect vascular maturation, but led to reduced fibrosis. Inhibition of TGF-β signaling after MI has adverse or beneficial effects on remodeling, depending on timing of inhibition.…”

“…Inhibition of TGF-β signaling after MI has adverse or beneficial effects on remodeling, depending on timing of inhibition. 15,16 The studies by Alex et al 11 and Quijada et al 14 point to pericyte activation as a novel TGF-β-dependent process regulating post-MI remodeling. In the future, it will be important to selectively target profibrotic and proangiogenic properties of pericytes to improve remodeling after MI.…”

Letter by Teng et al Regarding Article, “Cardiac Pericytes Acquire a Fibrogenic Phenotype and Contribute to Vascular Maturation After Myocardial Infarction”

“…However, deletion of the Tgfbr1 in cells expressing Cspg4 (chondroitin sulfate proteoglycan 4) may reduce fibrosis after MI, leading to a transient improvement in cardiac ejection fraction. 3 Additionally, after MI, cardiac pericytes exhibit timeregulated induction of genes associated with vascular permeability, generation of extracellular matrix, degradation of the basement membrane, and the TGF-β signaling pathway. Cardiac pericytes experience a spectrum of changes after MI.…”

Response by Frangogiannis to Letter Regarding Article, “Cardiac Pericytes Acquire a Fibrogenic Phenotype and Contribute to Vascular Maturation After Myocardial Infarction”

“…As Teng et al point out, the in vivo findings from genetically targeted mice suggest that TGF-β may mediate both fibrosis and vascular maturation in the infarcted heart. 1,2 Our study used inducible pericytespecific TGFBR2 (transforming growth factor β receptor 2) knockout mice, to demonstrate a central reparative role for TGF-β-induced activation of mural cells, mediated through stimulation of vascular maturation in the healing infarct. 1 On the other hand, Quijada et al 2 generated mice with pericyte-specific TGFBR1 (transforming growth factor β receptor 1) loss (using the same Cspg4 [chondroitin sulfate proteoglycan 4]-CreER driver) and demonstrated fibrogenic actions of TGF-β on pericytes that may contribute to dysfunction.…”