Alterations of Arterial Physiology in Osteopontin-Null Mice

Abstract

OBJECTIVE: In this study, we characterized the effects of an osteopontin (OPN)-null mutation in normal arterial function and remodeling in a murine model. METHODS AND RESULTS: OPN-null mutant mice were compared with wild-type mice before and after carotid artery ligation. Before ligation, OPN-null mice had increased heart rate, lower blood pressure, and increased circulating lymphocytes compared with wild-type mice. OPN-null vessels also demonstrated greater compliance accompanied by a loosely organized collagen network. After carotid artery ligation, significant differences were also found in the remodeling response of OPN-null animals. At 4 days after ligation, leukocyte adhesion/invasion was diminished by 10-fold in OPN-null mice compared with wild-type mice. At 14 days after ligation, the ligated arteries of OPN-null mice had smaller neointimal lesions but greater constrictive remodeling compared with wild-type mice, resulting in similar lumen areas. Continued remodeling resulted in a similar morphological phenotype in both groups at 28 days. CONCLUSIONS: These data show that endogenous OPN regulates normal vascular physiology and contributes to the vascular remodeling response by regulating vascular compliance and the inflammatory response.