Deciphering actin cytoskeletal function in the contractile vascular smooth muscle cell

Abstract

This review focuses on the vascular smooth muscle cells present in the medial layer of the blood vessels wall in the fully differentiated state (dVSMCs). The dVSMC contractile phenotype enables these cells to respond in a highly regulated manner to changes in extracellular stimuli. Through modulation of vascular contractile force and vascular compliance dVSMCs regulate blood pressure and blood flow. The cellular and molecular mechanisms by which vascular smooth muscle contractile functions are regulated are not completely elucidated. Recent studies have documented a critical role for actin polymerization and cytoskeletal dynamics in the regulation of contractile function. Here we will review the current understanding of actin cytoskeletal dynamics and focal adhesion function in dVSMCs in order to better understand actin cytoskeleton connections to the extracellular matrix and the effects of cytoskeletal remodelling on vascular contractility and vascular stiffness in health and disease.

Figure 1. Actin isoforms in dVSMCs

Freshly isolated aortic smooth muscle cells were fixed and stained with anti-α, β and cytoplasmic γ actin antibodies. Shown is a deconvolution microscopy centre optical section of: A, γ actin filaments (red), primarily located in the cell cortex; B, β actin filaments (green), primarily located in the cell interior as well as punctate staining in the cell cortex; and C, α smooth muscle actin (green) in filamentous structures twisting through the length of the cell. Nuclei visualized by DAPI staining (blue). Calibration bar, 10 μm in all panels. Reproduced with permission from Gallant et al. 2011.

Figure 2. Tropomyosin isoforms Tm1 and Tm6 in isolated dVSMCs

Freshly isolated aortic dVSMCs were fixed and stained to identify Tm1 (green, top panel) and Tm6 (green, bottom panel). Co-staining with phalloidin for identifies total actin (red, top panel). Co-staining for α actinin identifies focal adhesions and dense bodies (red, bottom panel). Reproduced with permission from Lehman & Morgan, 2012.

Figure 3. Schematic model of cytoskeletal organization in aortic dVSMCs

γ Actin mostly in the cell cortex and β actin surrounding the dense bodies and focal adhesions. Symbols and colours as indicated in box.