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Natriuretic Peptide Receptor 2 Locus Contributes to Carotid Remodeling.
Vyacheslav A Korshunov1, Elaine M Smolock1, Mary E Wines-Samuelson1
1Department of Medicine Aab Cardiovascular Research Institute Rochester NY.
Journal of the American Heart Association
|May 13, 2020
Summary
Genetic factors influence carotid artery intima/media thickness (IMT), a marker for cardiovascular events. Natriuretic peptide receptor 2 (Npr2) plays a key role in regulating vascular fibrosis and carotid remodeling, particularly in males.
Area of Science:
- Genetics
- Cardiovascular Biology
- Vascular Biology
Background:
- Carotid artery intima/media thickness (IMT) is a significant predictor of cardiovascular events.
- Genetic regulation of IMT is crucial for understanding cardiovascular disease risk.
Purpose of the Study:
- To identify novel genes regulating carotid IMT using genome-wide association studies.
- To investigate the role of candidate genes in carotid artery remodeling.
Main Methods:
- Genome-wide association study in 30 inbred mouse strains with induced carotid artery IMT.
- Histological analysis of carotid artery components and intima-to-media ratios.
- Genetic analysis of natriuretic peptide receptor 2 (Npr2) knockout mice and human atherosclerotic plaques.
Main Results:
- Significant variations in carotid artery morphology and remodeling were observed across mouse strains.
- Distinct genomic loci, including Npr2, were associated with carotid IMT traits.
- Npr2 deficiency in male mice led to defective carotid remodeling and increased fibrosis, with decreased Npr2 expression in human plaques.
Conclusions:
- Carotid IMT is regulated by multiple distinct genetic factors.
- Npr2 plays a critical role in the genetic control of vascular fibrosis and carotid artery remodeling, with sex-specific effects.
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