Differential effect of experimental hypertension and hypercholesterolemia on adventitial remodeling

Objective - 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. Method and Results - 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. Conclusions - 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.