on December 9, 2004
Published online before print December 9, 2004, doi: 10.1161/01.ATV.0000152606.34120.97
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Submitted on May 11, 2004
Accepted on November 1, 2004
Differential Effect of Experimental Hypertension and Hypercholesterolemia on Adventitial Remodeling
Joerg Herrmann ;
From the Division of Cardiovascular Diseases (J.H., S.S., A.L.) and the Division of Nephrology and Hypertension (A.C., M.R.P., L.O.L.), Department of Internal Medicine, Mayo Clinic Rochester, Minn.
* To whom correspondence should be addressed. E-mail: lerman.amir{at}mayo.edu.
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.
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