Role of the LDL Receptor-Related Protein 1 in Regulating Protease Activity and Signaling Pathways in the Vasculature

摘要

Aortic aneurysms represent a significant clinical problem as they largely go undetected untila rupture occurs. Currently, an understanding of mechanisms leading to aneurysm formation is limited.Numerous studies clearly indicate that vascular smooth muscle cells play a major role in the developmentand response of the vasculature to hemodynamic changes and defects in these responsescan lead to aneurysm formation. The LDL receptor-related protein 1 (LRP1) is major smooth musclecell receptor that has the capacity to mediate the endocytosis of numerous ligands and to initiate andregulate signaling pathways. Genetic evidence in humans and mouse models reveal a critical role forLRP1 in maintaining the integrity of the vasculature. Understanding the mechanisms by which this isaccomplished represents an important area of research, and likely involves LRP1’s ability to regulatelevels of proteases known to degrade the extracellular matrix as well as its ability to modulate signalingevents.