Title:Role of the LDL Receptor-Related Protein 1 in Regulating Protease Activity and Signaling Pathways in the Vasculature
VOLUME: 19 ISSUE: 11
Author(s):Dianaly T. Au, Allison L. Arai, William E. Fondrie, Selen C. Muratoglu* and Dudley K. Strickland*
Affiliation:Center for Vascular and Inflammatory Diseases, Biopark I, R213, 800 W. Baltimore Street, Baltimore, Maryland 21201, MD, Center for Vascular and Inflammatory Diseases, Biopark I, R213, 800 W. Baltimore Street, Baltimore, Maryland 21201, MD, Center for Vascular and Inflammatory Diseases, Biopark I, R213, 800 W. Baltimore Street, Baltimore, Maryland 21201, MD, Center for Vascular and Inflammatory Diseases, Biopark I, R213, 800 W. Baltimore Street, Baltimore, Maryland 21201, MD, Center for Vascular and Inflammatory Diseases, Biopark I, R213, 800 W. Baltimore Street, Baltimore, Maryland 21201, MD
Keywords:Lipoprotein receptors, LRP1, proteases, aneurysms, smooth muscle cells, extracellular matrix.
Abstract:Aortic aneurysms represent a significant clinical problem as they largely go undetected until
a 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 development
and response of the vasculature to hemodynamic changes and defects in these responses
can lead to aneurysm formation. The LDL receptor-related protein 1 (LRP1) is major smooth muscle
cell receptor that has the capacity to mediate the endocytosis of numerous ligands and to initiate and
regulate signaling pathways. Genetic evidence in humans and mouse models reveal a critical role for
LRP1 in maintaining the integrity of the vasculature. Understanding the mechanisms by which this is
accomplished represents an important area of research, and likely involves LRP1’s ability to regulate
levels of proteases known to degrade the extracellular matrix as well as its ability to modulate signaling
events.