Variation of mechanical properties and quantitative proteomics of VSMC along the arterial tree

Abstract

Vascular smooth muscle cells (VSMCs) are thought to assume a quiescent and homogeneous mechanical behavior after arterial tree development phase. However, VSMCs are known to be molecularly heterogeneous in other aspects and their mechanics may play a role in pathological situations. Our aim was to evaluate VSMCs from different arterial beds in terms of mechanics and proteomics, as well as investigate factors that may influence this phenotype. VSMCs obtained from seven arteries were studied using optical magnetic twisting cytometry (both in static state and after stretching) and shotgun proteomics. VSMC mechanical data were correlated with anatomical parameters and ultrastructural images of their vessels of origin. Femoral, renal, abdominal aorta, carotid, mammary, and thoracic aorta exhibited descending order of stiffness (G, P < 0.001). VSMC mechanical data correlated with the vessel percentage of elastin and amount of surrounding extracellular matrix (ECM), which decreased with the distance from the heart. After 48 h of stretching simulating regional blood flow of elastic arteries, VSMCs exhibited a reduction in basal rigidity. VSMCs from the thoracic aorta expressed a significantly higher amount of proteins related to cytoskeleton structure and organization vs. VSMCs from the femoral artery. VSMCs are heterogeneous in terms of mechanical properties and expression/organization of cytoskeleton proteins along the arterial tree. The mechanical phenotype correlates with the composition of ECM and can be modulated by cyclic stretching imposed on VSMCs by blood flow circumferential stress.

Segmental and age differences in the elastin network, collagen, and smooth muscle phenotype in the tunica media of the porcine aorta

“…For example, Guo and Kassab (2004) observed a lower stretch ratio and Cauchy stress in the porcine thoracic aorta, and Roach and Song (1994) observed that the abdominal aorta tears more easily while needing higher pressure for propagation of the defect when liquid is injected into the tunica media. Dinardo et al (2014) observed higher stiffness in the abdominal aorta due to reduced elastin content. In addition to the mechanical function of elastin in the aortic wall, this protein might be important in the progression of inflammatory changes because Lannoy et al (2014) observed elastin, together with fibrillin, acts as an autocrine factor that regulates the activity and availability of TGFs within the tissue.…”

“…Guo and Kassab, 2004;Sokolis et al, 2008;Dinardo et al, 2014). Most authors directly attributed the differences in the mechanical behavior of the aortic wall to different elastin content in the tunica media.…”

Differences in genetic signaling, and not mechanical properties of the wall, are linked to ascending aortic aneurysms in fibulin-4 knockout mice

“…It is also still not well understood why 60% of TAAs occur in the AA. Susceptibility of different vascular regions to TAAs has been attributed to locational differences in blood flow (10), endothelial permeability (42), ECM content and SMC mechanical properties (20), SMC gene expression (88), SMC embryonic origin (53), or SMC response to signaling molecules (60,80). Fibulin-4 knockout (Fbln4 Ϫ/Ϫ ) mice display opposite vascular phenotypes depending on the thoracic location, with aneurysms developing in the AA and narrowing occurring in the descending aorta (DA) (34,55), and represent a unique model to study differences in TAA susceptibility of specific locations.…”

Artery buckling stimulates cell proliferation and NF-κB signaling

“…It is well known that aging affects arterial structure and function (31,40). Arterial wall stiffness increases with aging due to increases in collagen content and cross-linking, a high collagen-to-elastin ratio, increased medial wall thickness, and vascular calcification (9,10,12,30,31). In addition, it has been reported that sex affects the mechanical properties, biochemical contents, and wall structure of arteries (41).…”