Molecular mechanisms of the vascular responses to haemodynamic forces

Abstract

Blood vessels are permanently subjected to mechanical forces in the form of stretch, encompassing cyclic mechanical strain due to the pulsatile nature of blood flow and shear stress. Significant variations in mechanical forces, of physiological or physiopathological nature, occur in vivo. These are accompanied by phenotypical modulation of smooth muscle cells and endothelial cells, producing structural modifications of the arterial wall. In all the cases, vascular remodelling can be allotted to a modification of the tensional strain or shear, and underlie a trend to reestablish baseline mechanical conditions. Vascular cells are equipped with numerous receptors that allow them to detect and respond to the mechanical forces generated by pressure and shear stress. The cytoskeleton and other structural components have an established role in mechanotransduction, being able to transmit and modulate tension within the cell via focal adhesion sites, integrins, cellular junctions and the extracellular matrix. Mechanical forces also initiate complex signal transduction cascades, including nuclear factor-jB and mitogen-activated protein kinase pathways, leading to functional changes within the cell.

Primary cilia sensitize endothelial cells for fluid shear stress

“…In addition, it can provide cells with directional information about blood flow to which EC respond with reorientation to the local shear axis (Topper and Gimbrone, 1999;Noria et al, 2004). Mechanical deformation of the cytoskeleton also links the apparently non-related shear sensors that have been described to date, including integrins, cell-cell adhesion molecules, tyrosine kinase receptors, G protein-coupled receptors, and ion channels for Ca 2ϩ and K ϩ (Lehoux et al, 2006;Li et al, 2005;Nauli et al, 2008). All these proteins are connected to the cytoskeleton, either directly or through linker proteins.…”

Dependence of Aortic Arch Morphogenesis on Intracardiac Blood Flow in the Left Atrial Ligated Chick Embryo

“…Shear stress patterns may change due to abnormal flow. Endothelial cells may respond to altered shear stress by the regulation of cell growth by integrins, the expression of growth factor, and cytoskeletal rearrangement (Gittenberger-de Groot et al, 2006;Lehoux et al, 2006;Linask and Vanauker, 2007;Groenendijk et al, 2008). Hogers et al confirmed that numerous unique streams of blood flow coursed between the embryonic heart and the extraembryonic vascular bed (Hogers et al, 1995).…”

The effect of mechanical strain on soft (cardiovascular) and hard (bone) tissues

“…The proteins present at focal adhesion become phosphorylated on tyrosine when the cells are stimulated, a FAK activation is an indicator in focal adhesion formation. 39,40 Up cell attachment to ECM proteins, integrins became activated and form cluster at the cell surface thus initiating the formation of adhesion complexes which will enhance FAK's catalytic activity and increase FAK tyrosine phosphorylation. FAK phosphorylation at tyrosine 397 (Y 397 ) leads to the recruitment of Src and Src-family kinases as well as to an increased phosphorylation of other proteins present in the adhesion complex such as paxilin and p130Cos.…”