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Review
. 2019 Apr 25;1(1):H23-H31.
doi: 10.1530/VB-19-0007. eCollection 2019.

Pericytes in the infarcted heart

Linda Alex  1 , Nikolaos G Frangogiannis  1
Affiliations
Review

Pericytes in the infarcted heart

Linda Alex et al. Vasc Biol. .

Abstract

The adult mammalian heart lacks regenerative capacity and heals through activation of an inflammatory cascade that leads to the formation of a collagen-based scar. Although scar formation is important to preserve the structural integrity of the ventricle, unrestrained inflammation and excessive fibrosis have been implicated in the pathogenesis of adverse post-infarction remodeling and heart failure. Interstitial cells play a crucial role in the regulation of cardiac repair. Although recent studies have explored the role of fibroblasts and immune cells, the cardiac pericytes have been largely ignored by investigators interested in myocardial biology. This review manuscript discusses the role of pericytes in the regulation of inflammation, fibrosis and angiogenesis following myocardial infarction. During the inflammatory phase of infarct healing, pericytes may regulate microvascular permeability and may play an important role in leukocyte trafficking. Moreover, pericyte activation through Toll-like receptor-mediated pathways may stimulate cytokine and chemokine synthesis. During the proliferative phase, pericytes may be involved in angiogenesis and fibrosis. To what extent pericyte to fibroblast conversion and pericyte-mediated growth factor synthesis contribute to the myocardial fibrotic response remains unknown. During the maturation phase of infarct healing, coating of infarct neovessels with pericytes plays an important role in scar stabilization. Implementation of therapeutic approaches targeting pericytes in the infarcted and remodeling heart remains challenging, due to the lack of systematic characterization of myocardial pericytes, their phenotypic heterogeneity and the limited knowledge on their functional role.

Keywords: angiogenesis; fibrosis; inflammation; myocardial infarction; pericyte.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review.

Figures

Figure 1
Figure 1
The adult mouse heart contains abundant pericytes. The immunofluorescence panels show myocardial sections from normal adult NG2Dsred reporter mice, stained for Griffonia Simplicifolia lectin (GSIL4) to identify endothelial cells (A), and for α-SMA to label vascular smooth muscle cells (B). A significant population of NG2+/α-SMA- peri-endothelial cells is noted (arrows). Arteriolar vascular smooth muscle cells express both NG2 and α-SMA (arrowheads).
Figure 2
Figure 2
The role of endogenous pericytes in myocardial infarction. The adult mammalian heart lacks regenerative capacity and heals through formation of a collagen-based scar. The reparative response can be divided into three distinct, but overlapping phases: the inflammatory phase, the proliferative phase and the maturation phase. The normal myocardium contains a large population of pericytes with peri-endothelial location. During the inflammatory phase, release of alarmins from dying cells may activate TLR-mediated pathways in pericytes, stimulating cytokine and chemokine secretion. Moreover, pericytes may produce matrix metalloproteinases, thus degrading the microvascular basement membrane and stimulating an angiogenic response. Formation of gaps between pericytes in the pro-inflammatory environment of the infarct may be required for leukocyte extravasation. Pericytes also regulate microvascular function. Constriction of pericytes in the ischemic and reperfused myocardium has been implicated in the pathogenesis of ‘no-reflow’. During the proliferative phase, pericytes activated by growth factors may regulate angiogenesis and fibrosis. To what extent pericyte to fibroblast conversion contributes to the expansion of myofibroblasts in healing infarcts remains unclear. Pericytes may also produce angiogenic and fibrogenic growth factors. During the maturation phase infarct neovessels recruit mural cells (both pericytes and vascular smooth muscle cells) through PDGFRβ-dependent pathways. Acquisition of a mural cell coat may be important to stabilize the infarct vasculature and to protect the infarcted heart from sustained inflammation.
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