Blood pressure-induced physiological strain variability modulates wall structure and function in aorta rings

Abstract

Vascular smooth muscle cells respond to mechanical stretch by reorganizing their cytoskeletal and contractile elements. Recently, we showed that contractile forces in rat aorta rings were maintained when the rings were exposed to 4 h of physiological variability in cycle-by-cycle strain, called variable stretch (VS), mimicking beat-to-beat blood pressure variability. Contractility, however, was reduced when the aorta was exposed to monotonous stretch (MS) with an amplitude equal to the mean peak strain of VS. Objective Here we reanalyzed the data to obtain wall stiffness as well as added new histologic and inhibitor studies to test the effects of VS on the extracellular matrix. Main results The results demonstrate that while the stiffness of the aorta did not change during 4 h MS or VS, nonlinearity in mechanical behavior was slightly stronger following MS. The inhibitor studies also showed that mitochondrial energy production and cytoskeletal organization were involved in this fluctuation-driven mechanotransduction. Reorganization of β-actin in the smooth muscle layer quantified from immunohistochemically labeled images correlated with contractile forces during contraction. Histologic analysis of wall structure provided evidence of reorganization of elastin and collagen fibers following MS but less so following VS. The results suggested that the loss of muscle contraction in MS was compensated by reorganization of fiber structure leading to similar wall stiffness as in VS. Significance We conclude that muscle tone modulated by variability in stretch plays a role in maintaining aortic wall structural and mechanical homeostasis with implications for vascular conditions characterized by a loss or an increase in blood pressure variability.

Harmonic Distortion of Blood Pressure Waveform as a Measure of Arterial Stiffness

“…This overlap is largely originated from increased speed of both wavelets, coupled with earlier reflections during arterial remodeling ( van Varik et al, 2012 ). Spectral decomposition of stress waveforms via a Fourier transform has been used in a previous study to characterize mechanical nonlinearity of isolated rat aorta ( Imsirovic et al, 2018 ). Future study is required to understand the role of nonlinear arterial wall properties in relation to HD.…”

Tuning mitochondrial structure and function to criticality by fluctuation-driven mechanotransduction

“…For example, the contractile apparatus of VSMCs is down-regulated by V0 compared to V25 which results in a reduced contractile force in vascular walls 24 . In the absence of natural BPV, the reduced VSMC contractility also substantially alters arterial wall ECM structure 63 . Alternatively, too much variability as in the case of V50, a fragmented mitochondrial network emerges with increased ROS production (Figs.…”

Regional functional and structural abnormalities within the aorta as a potential driver of vascular disease in metabolic syndrome

“…The pathogenesis of vascular disease in the context of metabolic syndrome is complex and likely to result from an interaction between functional and mechanical components. Changes in vascular smooth muscle contractility can result in varying degrees of stretching of the aortic wall, leading to subsequent changes in aortic structure and mechanical components (Imsirovic et al., 2018), with resultant changes in blood pressure, which in turn further exacerbate the vascular abnormalities.…”