Regulation and characteristics of vascular smooth muscle cell phenotypic diversity

Abstract

Vascular smooth muscle cells can perform both contractile and synthetic functions, which are associated with and characterised by changes in morphology, proliferation and migration rates, and the expression of different marker proteins. The resulting phenotypic diversity of smooth muscle cells appears to be a function of innate genetic programmes and environmental cues, which include biochemical factors, extracellular matrix components, and physical factors such as stretch and shear stress. Because of the diversity among smooth muscle cells, blood vessels attain the flexibility that is necessary to perform efficiently under different physiological and pathological conditions. In this review, we discuss recent literature demonstrating the extent and nature of smooth muscle cell diversity in the vascular wall and address the factors that affect smooth muscle cell phenotype. (Neth Heart J 2007;15:100-8.).

Figure 1

Ultrastructural characteristics of contractile and synthetic SMCs.

Figure 2

Schematic representation of expression levels of genes associated with a particular SMC phenotype. Note that most of the indicated proteins are not SMC specific.

Figure 3

Whereas the SMCs in a vessel can collectively cover the whole spectrum of phenotypes, a given population of SMCs (indicated by a to f, respectively) can only cover a limited area of this spectrum. The boundaries of the spectrum for any given SMC population are defined by (epi)genetic programmes. SMCs can modulate their phenotype within the boundaries, a process which is controlled by the integration of environmental factors.

Figure 4

Factors involved in vascular SMC development, differentiation and phenotypic modulation.

Figure 5

SMC differentiation pathways. SMC precursors first differentiate towards naive SMCs, which have a synthetic phenotype. The large majority of SMCs subsequently acquire a more contractile phenotype, although the extent of contractile differentiation differs and many cells retain a phenotype between synthetic and contractile. Both differentiated synthetic and differentiated contractile SMCs can reversibly change their phenotype via phenotypic modulation.