Mechanical programming of arterial smooth muscle cells in health and ageing

Abstract

Arterial smooth muscle cells (ASMCs), the predominant cell type within the arterial wall, detect and respond to external mechanical forces. These forces can be derived from blood flow (i.e. pressure and stretch) or from the supporting extracellular matrix (i.e. stiffness and topography). The healthy arterial wall is elastic, allowing the artery to change shape in response to changes in blood pressure, a property known as arterial compliance. As we age, the mechanical forces applied to ASMCs change; blood pressure and arterial wall rigidity increase and result in a reduction in arterial compliance. These changes in mechanical environment enhance ASMC contractility and promote disease-associated changes in ASMC phenotype. For mechanical stimuli to programme ASMCs, forces must influence the cell’s load-bearing apparatus, the cytoskeleton. Comprised of an interconnected network of actin filaments, microtubules and intermediate filaments, each cytoskeletal component has distinct mechanical properties that enable ASMCs to respond to changes within the mechanical environment whilst maintaining cell integrity. In this review, we discuss how mechanically driven cytoskeletal reorganisation programmes ASMC function and phenotypic switching.

Using Polyacrylamide Hydrogels to Model Physiological Aortic Stiffness Reveals that Microtubules Are Critical Regulators of Isolated Smooth Muscle Cell Morphology and Contractility

“…Matrix rigidity rapidly activates Rho/ROCK signalling at ECM adhesions, initiating actin polymerisation and myosin light chain phosphorylation, thereby augmenting actomyosin activity ( Ahmed and Warren, 2018 ). Actin cytoskeletal reorganisation and enhanced actomyosin activity increase VSMC integrated traction forces, the force VSMCs apply to the ECM ( Li et al, 2020 ; Johnson et al, 2021 ). While much is known about VSMC actomyosin and contractile responses, we still lack an understanding of how VSMC structural and signalling components integrate to regulate these processes.…”

“…Extracellular mechanical forces, generated by the flow of blood and the mechanical properties of the ECM, programme the function of VSMCs ( Johnson et al, 2021 ). In healthy arteries, VSMC contraction is initiated in response to blood pressure derived deformation of the arterial wall ( Ye et al, 2014 ).…”

“…Actomyosin derived contractile forces place stress and intracellular tension upon the cell. In other cell types, these deformational forces are proposed to be balanced by the ECM and the microtubule network ( Johnson et al, 2021 ). This relationship is described by the tensegrity model, whereby microtubules act as compression bearing struts, capable of resisting strain generated by the actin cytoskeleton ( Stamenović, 2005 ; Brangwynne et al, 2006 ).…”

Using polyacrylamide hydrogels to model physiological aortic stiffness reveals that microtubules are critical regulators of isolated smooth muscle cell morphology and contractility

“…These actomyosin derived contractile forces place stress and intracellular tension upon the cell. In other cell types, these deformational forces are proposed to be balanced by the ECM and the microtubule network (Johnson et al, 2021). This relationship is described by the tensegrity model, whereby microtubules act as compression bearing struts, capable of resisting strain generated by the actin cytoskeleton (Stamenović, 2005;Brangwynne et al, 2006).…”

Cardiovascular mechanobiology—a Special Issue to look at the state of the art and the newest insights into the role of mechanical forces in cardiovascular development, physiology and disease

“…Wang and Valdez-Jasso (2021) take a closer look at the mechanical regulation in pulmonary arterial hypertension, thoroughly discussing recent studies of endothelial cells, smooth muscle cells and fibroblasts in vitro, in vivo and in silico. The review from Johnson et al (2021) on the other hand discusses how mechanical forces affect the arterial smooth muscle cell cytoskeleton, which eventually projects on cellular phenotype and contractility. From a bioengineering perspective, Nguyen et al (2021) provide a detailed review of microfluidic platforms for studying the mechanobiology of human circulatory system, while Herault et al (2021) look at the role of miRNAs and their regulation into clusters and families in vascular mechanobiology.…”