Contributors: Luciano Capettini, Rafaela Fernandes da Sliva (Group leader)
Collaborators: Prof. R. Santos, UFMG, Brazil; Prof. F. Mach and Dr. F. Montecucco, U. of Geneva
Hemodynamic forces are key regulators of cell behaviour and function. However, the processes by which forces are transduced to biochemical signals and translated into downstream effects are poorly understood.
Wall shear stress, the frictional force generated by blood flow, is considered as one of the major forces acting on the endothelium and an important factor to maintain vascular homeostasis. Alterations on wall shear stress induce changes on EC morphology, activate the expression of proinflammatory genes and chemoattractant cytokines, priming the endothelium to the development of early atherosclerotic lesions and cerebral aneurysm. More recently, local low shear stress values has been identified as a determinant biomechanical stimulus in the conversion of stable to unstable plaque.
In addition to shear stress, EC and vascular smooth muscle cell (VSMC) are constantly exposed to cyclic stretch, which is the force resulted from the pulsatile nature of pressure. Alterations on cyclic stretch affect VSMC phenotype, proliferation and migration. These processes are known to be involved in atherosclerosis, in hypertension and in natural vascular aging.
In our laboratory we developed and applied highly controllable models to investigate new pathways implicated in the cause-effect relationship between individual hemodynamic forces and the development of vascular diseases:
• In vitro perfusion model of EC cultured on silicon tube
• Ex vivo perfusion of arterial segments
• In vivo model of shear stress-induced atherogenesis and plaque vulnerability