Cellular Crosstalk between Endothelial and Smooth Muscle Cells in Vascular Wall Remodeling.

Nerea Méndez-Barbero,Luis Blanco-Colio,Carmen Gutiérrez-Muñoz

doi:10.3390/ijms22147284

Abstract

Pathological vascular wall remodeling refers to the structural and functional changes of the vessel wall that occur in response to injury that eventually leads to cardiovascular disease (CVD). Vessel wall are composed of two major primary cells types, endothelial cells (EC) and vascular smooth muscle cells (VSMCs). The physiological communications between these two cell types (EC–VSMCs) are crucial in the development of the vasculature and in the homeostasis of mature vessels. Moreover, aberrant EC–VSMCs communication has been associated to the promotor of various disease states including vascular wall remodeling. Paracrine regulations by bioactive molecules, communication via direct contact (junctions) or information transfer via extracellular vesicles or extracellular matrix are main crosstalk mechanisms. Identification of the nature of this EC–VSMCs crosstalk may offer strategies to develop new insights for prevention and treatment of disease that curse with vascular remodeling. Here, we will review the molecular mechanisms underlying the interplay between EC and VSMCs. Additionally, we highlight the potential applicable methodologies of the co-culture systems to identify cellular and molecular mechanisms involved in pathological vascular wall remodeling, opening questions about the future research directions.

Highlights

IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
We summarized the different pathways of cell–cell communication as well as the different in vitro models to analyze endothelial cells (EC)–vascular smooth muscle cells (VSMCs) interaction
When a mechanical/chemical injury or loss of the endothelium take place, there is a disturbed crosstalk between EC and VSMCs, that would trigger VSMCs phenotypic and functional changes, inflammation, and extracellular matrix (ECM) deposition, all of them featuring the pathological vascular wall remodeling [8]

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Due to our lifestyle in which we are exposed to many cardiovascular risk factors (such as smoking, hypertension, cholesterol diet, sedentary life style, stress, or pollution), a high percentage of the population have developed an asymptomatic vascular damage, affecting the vascular homeostasis This high mortality rate indicates the need to identify the molecular mechanisms that occur during the pathogenesis of CVD, in order to develop new strategies for the early diagnosis and treatment to avoid the fatal ending. This remodeling is an active process that involves changes in the proliferative and migratory status of VSMCs, endothelial dysfunction, inflammatory processes, as well as synthesis or degradation of the components of the extracellular matrix (ECM) [12] All these processes are regulated by the dynamic interaction of growth factors, vasoactive substances, and hemodynamic stimuli between cells, which trigger changes in the structure and functionality of the vascular wall [13,14]. We summarized the different pathways of cell–cell communication as well as the different in vitro models to analyze EC–VSMCs interaction

EC–VSMC Communication

Paracrine Communications

Contact-Contact Signaling

In Vitro Models to Study EC–VSMCs Communication during Vascular Remodeling