MMP12 preferentially attenuates axial stiffening of aging arteries

J Biomech Eng. 2019 Mar 27;141(8):0810041-0810049. doi: 10.1115/1.4043322. Online ahead of print.

Abstract

Arterial stiffening is a hallmark of aging, but how aging affects the arterial response to pressure is still not completely understood, especially with regard to specific matrix metalloproteinases (MMPs). Here, we used pressure myography of carotid arteries from C57BL/6 mice to study the effects of age and MMP12, a major arterial elastase, on arterial biomechanics. Aging from 2 to 24 months leads to both circumferential and axial stiffening with stretch, and these changes are associated with an increased wall thickness, decreased inner radius, and a decreased in vivo axial stretch ratio (IVSR). Analysis of IVSR and stress-stretch curves with arteries from age- and sex-matched wild-type and MMP12-null arteries demonstrate that MMP12 deletion attenuates age-dependent arterial stiffening, mostly in the axial direction. MMP12 deletion also prevents the aging-associated decrease in the in vivo stretch ratio and, in general, leads to an axial mechanics phenotype characteristic of much younger mice. Circumferential arterial mechanics were much less affected by deletion of MMP12. We conclude that the induction of MMP12 during aging preferentially controls axial arterial mechanics.