Microvascular Smooth Muscle Cells Exhibit Divergent Phenotypic Switching Responses to Platelet-derived Growth Factor and Insulin-like Growth Factor 1

Overview

Journal Microvasc Res

Specialty Cardiology & Vascular Diseases

Date 2023 Sep 16

PMID 37716411

Authors

Marisa A Bickel

David M Sherry

Elizabeth C Bullen

Michaela L Vance

Ken L Jones

Eric W Howard

Shannon M Conley

Affiliations

Soon will be listed here.

Abstract

Objective: Vascular smooth muscle cell (VSMC) phenotypic switching is critical for normal vessel formation, vascular stability, and healthy brain aging. Phenotypic switching is regulated by mediators including platelet derived growth factor (PDGF)-BB, insulin-like growth factor (IGF-1), as well as transforming growth factor-β (TGF-β) and endothelin-1 (ET-1), but much about the role of these factors in microvascular VSMCs remains unclear.

Methods: We used primary rat microvascular VSMCs to explore PDGF-BB- and IGF-1-induced phenotypic switching.

Results: PDGF-BB induced an early proliferative response, followed by formation of polarized leader cells and rapid, directionally coordinated migration. In contrast, IGF-1 induced cell hypertrophy, and only a small degree of migration by unpolarized cells. TGF-β and ET-1 selectively inhibit PDGF-BB-induced VSMC migration primarily by repressing migratory polarization and formation of leader cells. Contractile genes were downregulated by both growth factors, while other genes were differentially regulated by PDGF-BB and IGF-1.

Conclusions: These studies indicate that PDGF-BB and IGF-1 stimulate different types of microvascular VSMC phenotypic switching characterized by different modes of cell migration. Our studies are consistent with a chronic vasoprotective role for IGF-1 in VSMCs in the microvasculature while PDGF is more involved in VSMC proliferation and migration in response to acute activities such as neovascularization. Better understanding of the nuances of the phenotypic switching induced by these growth factors is important for our understanding of a variety of microvascular diseases.

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