Abstract 515: Increased Adventitial Inflammation Occurs in Regions of Low Endothelial Shear Stress in a Swine Model of Coronary Atherosclerosis

Abstract

Introduction: Plaque inflammation is a critical step in the initiation and progression of atherosclerosis. Such inflammation is thought to originate from the luminal surface of plaque and infiltrate the intima-media in advanced lesions. Low endothelial shear stress (ESS) is known to induce intima-media inflammation and plaque growth. In this study we investigated in-vivo the hypothesis that low ESS induces also adventitial inflammation. Methods: We studied 11 swine at 23 (baseline) and 30 (followup) weeks after the induction of diabetes and hyperlipidemia. Using angiography and intravascular ultrasound data, we performed 3D coronary reconstruction of coronary arteries and calculated the ESS with computational fluid dynamics. In 56 segments, we assessed the adventitial inflammatory (CD45) and antigen-presenting (MHC-II) cell content at followup with immunohistochemistry. Segments were classified as low (≤ 1 Pa) or higher (>1 Pa) ESS. Results: MHC-II content in the adventitia (1.3±0.3%) was higher than in the media (0.3±0.1%, p<0.001) but lower than in the intima (9.3±2.3%, p<0.001). Low-ESS regions had increased adventitial MHC-II content compared to high-ESS regions (1.6±0.4 vs. 0.9±0.3%, p<0.05). Adventitial MHC-II content was not influenced by plaque size (large plaques 1.7±0.5 vs. intermediate plaques 0.8±0.3%, p=0.24), internal elastic lamina fragmentation (IEL) grade (minimal/absent 0.6±0.3 vs. moderate/large 1.4±0.3, p=0.9), or remodeling pattern (inadequate 1.7±0.6 vs. compensatory 1.2±0.4 vs. expansive 0.6±0.2%, p=0.6). Adventitial CD45 content was not significantly different between low- and high-ESS segments, and also not different in large vs. intermediate plaques, in segments with various IEL fragmentation grades or remodeling patterns. Conclusion: Although total inflammation is not dependent on ESS, low ESS induces higher adventitial activated inflammatory cell content, as assessed by MHC-II immunostaining. This, in conjunction with the higher MHC-II content in the adventitia than in the media and the presence of an intact IEL suggests an additional source of inflammation in low-ESS plaque regions, originating from the vessel outer wall. The induction of neovascularization possibly accounts for this phenomenon.