Assessment of the nano-mechanical properties of healthy and atherosclerotic coronary arteries by atomic force microscopy.

Nano-indentation techniques might be better equipped to assess the heterogeneous material properties of plaques than macroscopic methods but there are no bespoke protocols for this kind of material testing for coronary arteries. Therefore, we developed a measurement protocol to extract mechanical properties from healthy and atherosclerotic coronary artery tissue sections. Young's modulus was derived from force-indentation data. Metrics of collagen fibre density were extracted from the same tissue, and the local material properties were co-registered to the local collagen microstructure with a robust framework. The locations of the indentation were retrospectively classified by histological category (healthy, plaque, lipid-rich, fibrous cap) according to Picrosirius Red stain and adjacent Hematoxylin & Eosin and Oil-Red-O stains. Plaque tissue was softer (p < 0.001) than the healthy coronary wall. Areas rich in collagen within the plaque (fibrous cap) were significantly (p < 0.001) stiffer than areas poor in collagen/lipid-rich, but less than half as stiff as the healthy coronary media. Young's moduli correlated (Pearson's ρ = 0.53, p < 0.05) with collagen content. Atomic force microscopy (AFM) is capable of detecting tissue stiffness changes related to collagen density in healthy and diseased cardiovascular tissue. Mechanical characterization of atherosclerotic plaques with nano-indentation techniques could refine constitutive models for computational modelling.

Considering the Influence of Coronary Motion on Artery-Specific Biomechanics Using Fluid-Structure Interaction Simulation.

The endothelium in the coronary arteries is subject to wall shear stress and vessel wall strain, which influences the biology of the arterial wall. This study presents vessel-specific fluid-structure interaction (FSI) models of three coronary arteries, using directly measured experimental geometries and boundary conditions. FSI models are used to provide a more physiologically complete representation of vessel biomechanics, and have been extended to include coronary bending to investigate its effect on shear and strain. FSI both without- and with-bending resulted in significant changes in all computed shear stress metrics compared to CFD (p = 0.0001). Inclusion of bending within the FSI model produced highly significant changes in Time Averaged Wall Shear Stress (TAWSS) + 9.8% LAD, + 8.8% LCx, - 2.0% RCA; Oscillatory Shear Index (OSI) + 208% LAD, 0% LCx, + 2600% RCA; and transverse wall Shear Stress (tSS) + 180% LAD, + 150% LCx and + 200% RCA (all p < 0.0001). Vessel wall strain was homogenous in all directions without-bending but became highly anisotropic under bending. Changes in median cyclic strain magnitude were seen for all three vessels in every direction. Changes shown in the magnitude and distribution of shear stress and wall strain suggest that bending should be considered on a vessel-specific basis in analyses of coronary artery biomechanics.

Mechanosensitive pathways are regulated by mechanosensitive miRNA clusters in endothelial cells.

Shear stress is known to affect many processes in (patho-) physiology through a complex, multi-molecular mechanism, termed mechanotransduction. The sheer complexity of the process has raised questions how mechanotransduction is regulated. Here, we comprehensively evaluate the literature about the role of small non-coding miRNA in the regulation of mechanotransduction. Regulation of mRNA by miRNA is rather complex, depending not only on the concentration of mRNA to miRNA, but also on the amount of mRNA competing for a single mRNA. The only mechanism to counteract the latter factor is through overarching structures of miRNA. Indeed, two overarching structures are present miRNA families and miRNA clusters, and both will be discussed in details, regarding the latest literature and a previous conducted study focussed on mechanotransduction. Both the literature and our own data support a new hypothesis that miRNA-clusters predominantly regulate mechanotransduction, affecting 65% of signalling pathways. In conclusion, a new and important mode of regulation of mechanotransduction is proposed, based on miRNA clusters. This finding implicates new avenues for treatment of mechanotransduction and atherosclerosis.