Epicardial progenitor cells (EpiCs) have a crucial role in cardiac development and vasculature formation. Here we detected the expression of Angiotensin II (Ang II) receptors AT1 and AT2 on EpiCs and demonstrated that AngII could increase the expression of smooth muscle specific markers, including α-smooth muscle actin (α-SMA) and myosin heavy chain 11 (Myh11) in EpiCs. Moreover, the expression of α-SMA and Myh11 induced by Ang II was blocked by pretreatment of EpiCs with the AT1 receptor antagonist losartan, but not the AT2 receptor antagonist PD123319. We further showed that the AngII-induced cells showed significant contractile responses to carbachol. These results implied that AngII could effectively induce EpiCs to differentiate into vascular smooth muscle-like cells through the AT1 receptor.
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http://dx.doi.org/10.1016/j.bbrc.2016.10.122 | DOI Listing |
Circ Res
January 2025
Division of Molecular Cardiovascular Biology (A.K.Z.J., R.K.K., R.J.V., S.-C.J.L., S.L.K.B., Y.K., K.M.G., K.W., M.A.S., T.A.B., J.D.M.), Department of Pediatrics, University of Cincinnati and Cincinnati Children's Hospital Medical Center, OH.
Background: TCF21 (transcription factor 21) is a bHLH (basic helix-loop-helix) protein required for the developmental specification of cardiac fibroblasts (CFs) from epicardial progenitor cells that surround the embryonic heart. In the adult heart, TCF21 is expressed in tissue-resident fibroblasts and is downregulated in response to injury or stimuli leading to myofibroblast differentiation. These findings led to the hypothesis that TCF21 regulates fibroblast differentiation in the adult mammalian heart to affect fibrosis.
View Article and Find Full Text PDFNat Commun
November 2024
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, WI, USA.
Balancing between regenerative processes and fibrosis is crucial for heart repair, yet strategies regulating this balance remain a barrier to developing therapies. The role of Interleukin 11 (IL11) in heart regeneration remains controversial, as both regenerative and fibrotic functions have been reported. We uncovered that il11a, an Il11 homolog in zebrafish, can trigger robust regenerative programs in zebrafish hearts, including cardiomyocytes proliferation and coronary expansion, even in the absence of injury.
View Article and Find Full Text PDFJ Cell Signal
January 2024
Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth 81 Research Drive, Scarborough, Maine, USA.
Pro-angiogenic paracrine/autocrine signaling impacts myocardial repair in cell-based therapies. Activin A receptor-like type 1 (, ALK1) signaling plays a pivotal role in cardiovascular development and maintenance, but its importance in human-derived therapeutic cardiac cells is not well understood. Here, we isolated a subpopulation of human highly proliferative cells (hHiPCs) from adult epicardial tissue and found that they express ALK1, a high affinity receptor for bone morphogenetic protein-9 (BMP9), which signals via SMAD1/5 to regulate paracrine/autocrine signaling and angiogenesis.
View Article and Find Full Text PDFStem Cell Reports
October 2024
Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan. Electronic address:
Understanding the molecular mechanisms of epicardial epithelial-to-mesenchymal transition (EMT), particularly in directing cell fate toward epicardial derivatives, is crucial for regenerative medicine using human induced pluripotent stem cell (iPSC)-derived epicardium. Although transforming growth factor β (TGF-β) plays a pivotal role in epicardial biology, orchestrating EMT during embryonic development via downstream signaling through SMAD proteins, the function of SMAD proteins in the epicardium in maintaining vascular homeostasis or mediating the differentiation of various epicardial-derived cells (EPDCs) is not yet well understood. Our study reveals that TGF-β-independent SMAD3 expression autonomously predicts epicardial cell specification and lineage maintenance, acting as a key mediator in promoting the angiogenic-oriented specification of the epicardium into cardiac pericyte progenitors.
View Article and Find Full Text PDFJ Mol Cell Cardiol
November 2024
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address:
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