Arterial in Vitro Remodeling: Analysis Biomechanical and Biological Factors Influencing the Adaptive Response

Objective: Vascular remodeling is an adaptive response to variations in the hemodynamic environment acting on the arterial wall. Remodeling translates into changes of structure, geometry and mechanical properties of the artery. Our aim was to study the remodeling response of pig right common carotid arteries in vitro. Methods: In vivo right carotid arteries are exposed to a non-uniform hemodynamic environment and exhibit a strong wall asymmetry in the circumferential direction that allows the study of two regions separately, as the artery remodels under in vitro perfusion. Porcine right common carotid arteries were cultured during 1(n=6), 3 (n=6) or 8 (n=6) days in an in vitro organ culture system, at a constant perfusion pressure of 100 mmHg. Geometrical, histological, biomechanical and biological analysis of the perfused segments was performed at the end of each study. Results: Smooth muscle cell nuclei density and wall thickness remain constant along the culture periods. Elastin and collagen are significantly redistributed to equilibrate their relative content along the vessel circumference. The distensibility profile is significantly different at day 8. MMP-2 expression and activity increase significantly at day 3 and 8. Conclusion: The non-axisymmetric arterial wall adapts to a uniform hemodynamic environment by redistributing the structural components of the extracellular matrix. The changes of collagen and elastin density may result from a vascular remodeling process involving MMP-2 upregulation and enzymatic activity. The remodeling response results in a new vascular wall configuration more distensible at physiological pressures (30-120 mmHg) and stiffer at higher pressures.