Journal
CURRENT DRUG TARGETS
Volume 19, Issue 11, Pages 1276-1288Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1389450119666180511162048
Keywords
Lipoprotein receptors; LRP1; proteases; aneurysms; smooth muscle cells; extracellular matrix
Categories
Funding
- National Heart, Lung, and Blood Institute
- National Cancer Institute, the National Institutes of Health [R35 HL135743, F31 HL131293, F31CA213815]
- American Heart Association Scientist Development Award [15SDG244 70170]
- NATIONAL CANCER INSTITUTE [F31CA213815] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R35HL135743, F31HL131293] Funding Source: NIH RePORTER
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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.
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