Abstract 5952: Fibrotic Atherosclerotic Lesion Exacerbates Large Arterial Stiffening Following Aortic Constriction In Apolipoprotein E Deficient Mice

Abstract

Hypertension, particularly systolic hypertension, is known to be a major risk factor for the development of atheroma. The effects of aortic atheroma on large arterial stiffness remain unclear. We introduced pressure overload in apoE −/− mice by transverse (TAC) or abdominal aorta constriction (AAC) for a period of 12-weeks. TAC led to 107% and 119% increase of pulse pressure, and AAC led to 55% and 51% increase of pulse pressure in wild-type and apoE −/− mice, respectively (all P <0.01), accompanied by a 3–4 fold increase of lesion area in apoE −/− mice (19.2±3.9% in TAC and 15.9±4.0% in AAC vs. 5.2±0.9% in sham-operation, all P <0.05). The lesion area correlated significantly with pulse pressure, but not with mean blood pressure (Fig ). Interestingly, plaque in TAC mice was fibrotic, while plaque in mice subjected to AAC was lipid-rich with a histology associated with plaque instability (Fig ). Furthermore, Apoe −/− mice post-TAC showed a more stiffened aorta than wild-type counterparts, evidenced by a greater degree of reduction in augmentation time (6.5±0.2 ms vs. 7.7±0.5 ms, P <0.05) and a greater degree of increment in augmentation index (77±2% vs. 71±2%, P <0.05). However, no such differences were observed between large artery stiffness in wild-type and Apoe −/− mice post-AAC. Our results show that different features of plaques developed in TAC and AAC models differing in PP only, and fibrotic plaques in Apoe −/− mice with TAC were associated with more pronounced large arterial stiffening. Plaque with thick layer of smooth muscle cells (SMC) in TAC vs lipid-rich plaque in AAC. Arrows indicate the organized blood clot in the expanded adventitial tissue due to plaque rupture.