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