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Atherosclerosis in perlecan heterozygous mice
Reeba K Vikramadithyan1, Yuko Kako, Guangping Chen
1Department of Medicine, Columbia University, New York, NY 10032, USA.
Journal of Lipid Research
|July 20, 2004
Summary
Reducing perlecan, a key arterial proteoglycan, appears to lessen early atherosclerosis in mice. Further research is needed to understand perlecan's complex role in this cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Proteoglycan Research
- Atherosclerosis Pathogenesis
Background:
- Perlecan is the primary heparan sulfate proteoglycan in arteries, located in the subendothelial matrix.
- Perlecan is a major component of the extracellular matrix within atherosclerotic lesions.
- The hypothesis that lipoprotein association with perlecan promotes atherosclerosis was investigated.
Purpose of the Study:
- To test the atherogenic role of perlecan by studying atherosclerosis in mice with a heterozygous deletion of perlecan.
- To analyze the impact of reduced perlecan expression on lesion development in genetically modified mouse models.
Main Methods:
- Studied perlecan expression in mouse atherosclerotic lesions.
- Generated mice with a heterozygous deletion of perlecan.
- Crossed the perlecan deletion into apolipoprotein E (apoE) and LDL receptor knockout backgrounds to study atherosclerosis.
- Assessed lesion size and atherosclerosis development at different time points (12 and 24 weeks).
Main Results:
- Mice with heterozygous perlecan deletion showed reduced arterial wall perlecan expression.
- Chow-fed apoE null mice with a heterozygous perlecan deletion exhibited less atherosclerosis at 12 weeks.
- At 24 weeks and in the LDL receptor heterozygous background, perlecan knockout allele presence did not significantly alter lesion size.
Conclusions:
- Loss of perlecan appears to reduce atherosclerosis in early-stage lesions, potentially by decreasing lipoprotein retention.
- Perlecan may influence multiple processes that collectively accelerate atherosclerosis, warranting further investigation into its multifaceted roles.