Differential Effect of Experimental Hypertension and Hypercholesterolemia on Adventitial Remodeling

Abstract

Intima-media remodeling, as frequently assessed by changes in the external elastic lamina-to-lumen area (EELLA), is well-described in coronary artery disease in contrast to adventitial remodeling, especially in the early disease stage. Female domestic pigs were randomized to one of the following 12-week treatment groups: normal diet (N; n=6), high-cholesterol diet (HC; n=6), or renovascular hypertension (HT; n=4). Low-density lipoprotein (LDL) cholesterol serum concentration was higher in HC than in N and HT (395.5+/-106 versus 38.6+/-14 and 37.2+/-6.8 mg/dL; P<0.05 for both). Mean arterial pressure was higher in HT than in N and HC (141.3+/-21 versus 107.4+/-8.9 and 109.4+/-7.8 mm Hg; P<0.05 for both). EELLA ratio, as assessed by morphometry, was similar in N, HC, and HTN (1.03+/-0.32 versus 0.95+/-0.29 and 1.01+/-0.09; P<0.05 for both). Coronary vasa vasorum density, as assessed by 3-dimensional micro-computed tomography, was higher in HC than in N and HT (3.4+/-1.0 versus 1.9+/-0.3 and 2.0+/-1.2; P<0.05 for both). In contrast, immunostaining showed a higher collagen III content and the presence of adventitial myofibroblasts in HT compared with N and HC. The current study suggests that adventitial remodeling precedes intima and media remodeling of coronary arteries early after exposure to hypercholesterolemia and hypertension, with distinct qualitative differences between them. Intima-media remodeling is well-described in coronary artery disease in contrast to adventitial remodeling. Results of the current study on coronary arteries of pigs, randomized to 12 weeks of normal diet (N), hypercholesterolemic diet (HC), or renovascular hypertensive (HT), indicate that adventitial remodeling precedes intima-media remodeling early after risk factor exposure with distinct qualitative differences.