Physics Meets Molecules

Abstract

See related article, pages 538–545 Arteries and veins are permanently exposed to hemodynamic forces because of the pulsatile nature of blood pressure and flow. Hence, the endothelium is constantly detecting different biomechanical forces, cyclic stretch and shear stress in particular,1–2 and converts the latter stimuli into intra- and extracellular signals. Endothelial cells thereby modulate multiple of physiological and pathophysiological processes: production of growth-promoting and growth-inhibiting hormones, enzymes, cytokines, etc; mediation of inflammatory responses through the expression of chemotactic and adhesion molecules on the endothelial surface; modulation of hemostasis and thrombosis via secretion of procoagulant, anticoagulant, and fibrinolytic agents; and the regulation of vascular smooth muscle cell contraction through the release of vasodilators and vasoconstrictors.3–5 This being the case, the equilibrium between physiological levels of blood flow (shear stress) and the endothelium is tightly counterbalanced. Thereby, the lumen radius of an artery is the most important denominator, which signifies that the smaller the lumen the higher the shear stress. However, once physiological shear forces are reduced, several pathological conditions may arise: proatherogenic and/or prothrombotic states and hence atherosclerosis and/or thrombosis.6–7 Inversely, high levels of shear forces play a key role in adaptive phases of arteriogenesis (collateral artery growth), the most clinically relevant mechanism of vascular development.8 In case of an arterial stenosis, these arterial/arteriolar anastomoses are the only anastomosis to the low-pressure territory and perfuse the periphery with nutrient blood flow. Elevation of shear stress and concomitant cyclic stretch are currently discussed to be the strongest inducers of arteriogenesis. In a rabbit model of femoral artery ligation, Schaper and colleagues induced an abrupt increase in shear stress by means of an arterial–venous shunt (pressure drop across collateral arteries) and accelerated the speed of arteriogenesis, surpassing the conductance values of the occluded artery when shear …