Impact of genetic background and aging on mesenteric collateral growth capacity in Fischer 344, Brown Norway, and Fischer 344 x Brown Norway hybrid rats

Departments of 1 Surgery and 2 Cellular and Integrative Physiology, Indiana University School of Medicine, and 3 Indiana Center for Vascular Biology and Medicine, Indianapolis, Indiana Submitted 10 January 2007 ; accepted in final form 25 September 2007 Available studies indicate that both genetic background and aging influence collateral growth capacity, but it is not known how their combination affects collateral growth. We evaluated collateral growth induced by ileal artery ligation in Fischer 344 (F344), Brown Norway (BN), and the first generation hybrid of F344 x BN (F1) rats available for aging research from the National Institute on Aging. Collateral growth was determined by paired diameter measurements in anesthetized rats immediately and 7 days postligation. In 3-mo-old rats, significant collateral growth occurred only in BN (35% ± 11%, P < 0.001). The endothelial cell number in arterial cross sections was also determined, since this precedes shear-mediated luminal expansion. When compared with the same animal controls, the intimal cell number was increased only in BN rats (92% ± 21%, P < 0.001). The increase in intimal cell number and the degree of collateral luminal expansion in BN rats was not affected by age from 3 to 24 mo. Immunohistochemical studies demonstrated that intimal cell proliferation was much greater in the collaterals of BN than of F1 rats. The remarkable difference between these three strains of rats used in aging research and the lack of an age-related impairment in the BN rats are novel observations. These rat strains mimic clinical observations of interindividual variation in collateral growth capacity and the impact of age on arteriogenesis and should be useful models to investigate the molecular mechanisms responsible for such differences. strain dependent; endothelial proliferation; macrophage recruitment Address for reprint requests and other correspondence: J. L. Unthank, Dept. of Surgery (WD OPW 425E), Indiana Univ. Medical Ctr, 1001 W. 10th St., Indianapolis, IN 46202-2879 (e-mail: junthank{at}iupui.edu )