Mechanosignaling in the vasculature: emerging concepts in sensing, transduction and physiological responses

Abstract

Chatterjee S, Fujiwara K, Pérez NG, Ushio-Fukai M, Fisher AB. Mechanosignaling in the vasculature: emerging concepts in sensing, transduction and physiological responses. Am J Physiol Heart Circ Physiol 308: H1451-H1462, 2015. First published April 10, 2015; doi:10.1152/ajpheart.00105.2015.-Cells are constantly exposed to mechanical forces that play a role in modulating cellular structure and function. The cardiovascular system experiences physical forces in the form of shear stress and stretch associated with blood flow and contraction, respectively. These forces are sensed by endothelial cells and cardiomyocytes and lead to responses that control vascular and cardiac homeostasis. This was highlighted at the Pan American Physiological Society meeting at Iguassu Falls, Brazil, in a symposium titled "Mechanosignaling in the Vasculature." This symposium presented recent research that showed the existence of a vital link between mechanosensing and downstream redox sensitive signaling cascades. This link helps to transduce and transmit the physical force into an observable physiological response. The speakers showcased how mechanosensors such as ion channels, membrane receptor kinases, adhesion molecules, and other cellular components transduce the force via redox signals (such as reactive oxygen species and nitric oxide) to receptors (transcription factors, growth factors, etc.). Receptor activated pathways then lead to cellular responses including cellular proliferation, contraction, and remodeling. These responses have major relevance to the physiology and pathophysiology of various cardiovascular diseases. Thus an understanding of the complex series of events, from the initial sensing through the final response, is essential for progress in this field. Overall, this symposium addressed some important emerging concepts in the field of mechanosignaling and the eventual pathophysiological responses. Anrep effect; mechanotransduction; NADPH oxidase; revascularization; vasculature THIS ARTICLE is part of a collection on 1st PanAmerican Congress of Physiological Sciences: Physiology Without Borders. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http:// ajpheart.physiology.org/.Cells in vivo are constantly exposed to the physical forces associated with their local environment. Although it was well known that forces such as gravity and friction act on organisms and affect their function and structure, it is only in the last two decades that the complex processes by which these forces are sensed by cells is becoming clear (37,48,55,98). Cells and indeed cellular structures respond to external forces in a manner similar to chemical signaling where chemicals (ligands) bind to specific receptors on cells and initiate cellular signaling and an eventual response (24,26,36). Likewise, mechanical signaling or mechanotransduction involves the activation of receptors. Analogous to chemical signaling or chemotransduction, physical forces trigger a signaling proces...

Micropatterning as a tool to identify regulatory triggers and kinetics of actin-mediated endothelial mechanosensing

“…The sprouting of blood vessels from an existing vascular network involves the spatiotemporally coordinated degradation of and, thereafter invasion into, the surrounding extracellular matrix. This requires a careful sensing and then adaptation of the cell to changing biophysical properties (Chatterjee et al, 2015;Santos-Oliveira et al, 2015). Over the past years, the vast majority of work on endothelial mechanosensing has focused on vascular remodeling processes and altered redox signaling in response to fluid shear stress (Ando and Yamamoto, 2009;Chatterjee et al, 2015;Tzima et al, 2005).…”

“…This requires a careful sensing and then adaptation of the cell to changing biophysical properties (Chatterjee et al, 2015;Santos-Oliveira et al, 2015). Over the past years, the vast majority of work on endothelial mechanosensing has focused on vascular remodeling processes and altered redox signaling in response to fluid shear stress (Ando and Yamamoto, 2009;Chatterjee et al, 2015;Tzima et al, 2005). However, current knowledge on the physiological role and on the regulatory behavior of mechanosensitive signaling pathways in the context of angiogenesis is limited.…”

“…Apart from the morphological challenges imposed on cells during the migration in angiogenesis and wound healing, shear stress is among the most important extracellular forces encountered by the endothelium (Chatterjee et al, 2015). To verify our hypothesis that MRTF is more sensitive and/or relocalizes faster to a given mechanical stimulus than YAP, the subcellular localization of both transcription factors was analyzed under laminar flow conditions (Fig.…”

Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell signaling

“…We have investigated this response to reduced shear (that is, simulated ischemia) using an isolated lung preparation and isolated endothelial cells that have been flow adapted in vitro [149,150]. The loss of shear is sensed by a cell membrane complex (mechanosome) that is localized to caveolae; the mechanosome consists of platelet endothelial cell adhesion molecule (PECAM), vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial (VE)–cadherin, and possibly other elements [149,151]. The initial response to loss of shear is the inactivation of the inwardly-rectifying K ATP channels that results in cell membrane depolarization [149,152]; these channels are normally maintained in the open configuration by shear stress.…”

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“…To isolate the effects of only blood flow from those of O 2 , Fisher's group has established an in vivo model of pulmonary ischemia (by stopping only blood flow) in isolated and perfused rat lungs, where constant alveolar PO 2 (∼100 mmHg) was maintained by ventilation (Al-Mehdi et al, 1997;Song et al, 2001). Using this system, they identified that the cessation of blood flow was "sensed" by the endothelial cells and activated the "mechanosome" consisting of Platelet Endothelial Cell Adhesion Molecule (PECAM), VEGFR, and Vascular Endothelial (VE) cadherin (Chatterjee et al, 2014(Chatterjee et al, , 2015, to lead to the closure of K ATP channels (Olesen et al, 1988), and activation of NADPH oxidase 2 (NOX2) to generate reactive oxygen species (ROS) and nitric oxide, ultimately leading to oxidative injury (Chatterjee et al, 2008;Browning et al, 2012). Endothelial depolarization also resulted in opening Ca +2 channels with increased intracellular Ca +2 and activation of nitric oxide (NO) synthase, increase in NO, and consequent vasodilation (Chatterjee et al, 2014).…”