Developmental Biology of the Vascular Smooth Muscle Cell: Building a Multilayered Vessel Wall

Abstract

The assembly of the vessel wall from its cellular and extracellular matrix components is a critical process in the development and maturation of the cardiovascular system. However, fundamental questions concerning the origin of vessel wall cells and the mechanisms that regulate their development and differentiation remain unanswered. The initial step of vessel wall morphogenesis is formation of a primary vascular network, comprised of nascent endothelial cell tubes, via the processes of vasculogenesis and angiogenesis. Subsequently, primordial vascular smooth muscle cells (VSMCs) are recruited to the endothelium to form a multilayered vessel wall. During the course of development and maturation, the VSMC plays diverse roles: it is a biosynthetic, proliferative, and contractile component of the vessel wall. Although the field of vascular development has blossomed in the past decade, the molecules and mechanisms that regulate this developmental pathway are not well defined. The focus of this review is on those facets of VSMC development important for transforming a nascent endothelial tube into a multilayered structure. We discuss the primordial VSMC with particular attention to its purported origins, the components of the extracellular milieu that contribute to its development, and the contribution of embryonic hemodynamics to vessel wall assembly.

The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells

“…In fact, all the quail-to-chick proepicardial chimeric transplantation studies show a gradient in the expression of SMC markers from the media to the non-SMC adventitia of the coronaries. The close ontogenetic relationship between SMCs and fibroblasts has been discussed previously (Hungerford and Little, 1999). Finally, it has been demonstrated that non-epicardiallyderived fibroblasts can transdifferentiate and give rise to other cells types (Kon and Fujiwara, 1994).…”

Requirement of an Intermediate Gene Expression for Biphasic ERK1/2 Activation in Thrombin-stimulated Vascular Smooth Muscle Cells

“…The transition from a differentiated phenotype to a fibroblast-like proliferative state is observed during the onset or progression of atherosclerosis (2-3), one of the most common diseases in developed countries (4 -5). Under these conditions, the VSM cell phenotype is reminiscent of that observed during vascular development, where VSM cells play a key role in morphogenesis of the blood vessel and exhibit a high proliferative index, migrate, and produce extracellular matrix components (6). Conditions that promote the proliferative phenotype include the combined action of growth factors, proteolytic enzymes, and exposure to extracellular matrix proteins (7).…”

Dysmorphogenesis of Kidney Cortical Peritubular Capillaries in Angiopoietin-2-Deficient Mice

“…VSMC begin differentiation as "fibroblast-like" cells, lacking myofilaments and basement membranes and appearing as aggregates near embryonic EC. 25 Cell lineage studies in birds suggest that aortic arch VSMC are derived from ectoderm (ie, neural crest), whereas VSMC in other sites are mesodermally derived. However, there is also evidence that embryonic avian dorsal aortic EC transdifferentiate into myofilament-expressing mesenchymal cells.…”