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.