Vascular ageing impairs active modulation of murine aortic stiffness by smooth muscle cells.

Abstract

Background Ageing causes changes to arterial contractility and tissue microstructure, resulting in arterial stiffening, a strong risk factor for cardiovascular diseases. Because the interaction between these effects is largely unexplored, this study aims to investigate how ageing-induced changes in contractility and wall constituent microstructure impact arterial biomechanics in murine aortas. Methods Vasoreactive responses of thoracic descending aortas of adult (5-months-old, n=5) and old (24-months-old, n=5) C57Bl/6J mice to phenylephrine, N-Ω-Nitro-L-arginine methyl ester (L-NAME), and sodium nitroprusside were measured under dynamic pressurization conditions. Whole-vessel and individual-constituent biaxial viscoelastic properties were characterized during contraction and relaxation while mimicking physiological dynamic loading conditions. In addition, elastin fibers, collagen fibers, and smooth muscle nuclei microstructural organization and morphological properties were quantified in pressurized aortas using two-photon laser scanning microscopy. Results Compared to adult mice, aortas of old mice displayed thicker walls but similar pressure-diameter behaviors in the absence of contraction. Vasoconstriction in aortas of adult mice 1) significantly increased wall thickness, 2) reduced pulse wave velocity at physiologically high pressure ranges, 3) reduced circumferential and axial stresses and stiffnesses, and 4) altered constituent load bearing. Conversely, aortas of old mice exhibited reduced contractility, altered vasoreactive responses, and reduced cell density. As a result, they were uncapable to alter any of their biomechanical properties through vasoconstriction. Conclusion Vasoconstriction enables modulation of axial and circumferential stresses and stiffnesses in the adult mouse aorta. With ageing, this modulatory capacity was impaired.