Vascular wall protection

The vascular endothelium is under permanent hemodynamic frictional stress. Maintaining the integrity of the vasculature is essential for preventing aneurysmal dilatation and cholesterol infiltration, but the mechanisms involved in controlling vascular wall structure have been poorly understood. In April 11 Science, Philippe Boucher and colleagues at the University of Texas Southwestern Medical Center, Dallas, US, show that low-density lipoprotein receptor–related protein (LRP1) has a pivotal role in protecting vascular wall integrity and preventing atherosclerosis by controlling platelet-derived growth factor receptor (PDGFR) activation (Science, 300: 329-332, April 11, 2003).

Boucher et al. generated tissue specific knockout mice lacking LRP1 only in vascular smooth muscle cells (SMCs). They observed that inactivation of LRP1 in vascular SMCs of mice caused PDGFR overexpression and abnormal activation of PDGFR signaling. This resulted in disruption of the elastic layer, SMC proliferation, aneurysm formation, and marked susceptibility to cholesterol-induced atherosclerosis. They also showed that development of these ...