The Role of Mechanotransduction on Vascular Smooth Muscle Myocytes Cytoskeleton and Contractile Function

Abstract

Smooth muscle exhibits a highly organized structural hierarchy that extends over multiple spatial scales to perform a wide range of functions at the cellular, tissue, and organ levels. Early efforts primarily focused on understanding vascular smooth muscle function through biochemical signaling. However, accumulating evidence suggests that mechanotransduction, the process through which cells convert mechanical stimuli into biochemical cues, is requisite for regulating contractility. Cytoskeletal proteins that comprise the extracellular, intercellular, and intracellular domains are mechanosensitive and can remodel their structure and function in response to external mechanical cues. Pathological stimuli such as malignant hypertension can act through the same mechanotransductive pathways to induce maladaptive remodeling, leading to changes in cellular shape and loss of contractile function. In both health and disease, the cytoskeletal architecture integrates the mechanical stimuli and mediates structural and functional remodeling in the vascular smooth muscle.

Smooth muscle: a stiff sculptor of epithelial shapes

“…When smooth muscle cells contract, they can both shorten and increase their stiffnesses [25,26] through actomyosin contractility and through rearrangements of the cytoskeleton, for example, by repolymerizing actin [27]. The stiffness of a smooth muscle cell arises from its contractile network of actin fibres and myosin, along with its intermediate filament cytoskeleton of vimentin and desmin [28][29][30][31] (figure 1). Atomic force microscopy (AFM) studies on relaxed, dissected embryonic chicken gut sections have found that the muscular layer has a lower stiffness than the epithelium [32,33], but after contractile stimulation, individual smooth muscle cells can become at least twice as stiff as epithelial cells, even when muscle cells are prevented from physically shortening [34,35].…”

Structure of the Elastin-Contractile Units in the Thoracic Aorta and How Genes That Cause Thoracic Aortic Aneurysms and Dissections Disrupt This Structure

“…Contraction of the SMCs can influence blood flow in small arteries but does not play this role in aorta. 15, 16 Rather, SMC contraction may function as a mechanosensor in the aorta.…”

Noradrenaline has opposing effects on the hydraulic conductance of arterial intima and media

“…The dilatation of the ECM under SMC contraction is due to cell-generated forces pulling on the fibres of the ECM: contractile elements within SMCs are known to be mechanically connected to extracellular fibres (e.g. collagen) through integrins (Moiseeva, 2001, Ye et al, 2014, Bursa et al, 2011), causing a widening of intercellular channels as seen in Fig. 5 and increasing the strain in the matrix.…”