Low density lipoprotein receptor related protein 1 and abdominal aortic aneurysms.
OBJECTIVE
A recent GWAS demonstrated an association between low density lipoprotein receptor related protein 1 (LRP1) and abdominal aortic aneurysm (AAA). This review aims to identify how LRP1 may be involved in the pathogenesis of abdominal aortic aneurysm.


METHODS
A systematic review of the English language literature was undertaken in order to determine whether LRP1 and associated pathways were plausible candidates for contributing to the development and/or progression of AAA.


RESULTS
A comprehensive literature search of MEDLINE (since 1948), Embase (since 1980) and Health and Psychological Instruments (since 1985) was conducted in January 2012 identified 50 relevant articles. These studies demonstrate that LRP1 has a diverse range of biological functions and is a plausible candidate for playing a central role in aneurysmogenesis. Importantly, LRP1 downregulates MMP (matrix metalloproteinase) activity in vascular smooth muscle cells and regulates other key pathways involved in extracellular matrix remodelling and vascular smooth muscle migration and proliferation. Crucially animal studies have shown that LRP1 depletion leads to progressive destruction of the vascular architecture and aneurysm formation.


CONCLUSIONS
Published evidence suggests that LRP1 may play a key role in the development of AAA.
Department of Cardiovascular Sciences, University of Leicester, Leicester LE2 7LX, UK. bw69@le.ac.uk
J B
JB
Wild
P W
PW
Stather
N
N
Sylvius
E
E
Choke
R D
RD
Sayers
M J
MJ
Bown
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation
C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1