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A Model of Disturbed Flow-Induced Atherosclerosis in Mouse Carotid Artery by Partial Ligation and a Simple Method of RNA Isolation from Carotid Endothelium
11:00

A Model of Disturbed Flow-Induced Atherosclerosis in Mouse Carotid Artery by Partial Ligation and a Simple Method of RNA Isolation from Carotid Endothelium

Published on: June 22, 2010

Carotid artery atherosclerosis in hypertensive patients with a functional LDL receptor-related protein 6 gene variant

R Sarzani1, F Salvi, M Bordicchia

  • 1Department of Internal Medicine, "Hypertension Excellence Centre" of the European Society of Hypertension, University "Politecnica delle Marche", Ancona, Italy. r.sarzani@univpm.it

Nutrition, Metabolism, and Cardiovascular Diseases : NMCD
|October 17, 2009
PubMed

Insights

The common 1062V variant of Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) is a significant risk factor for carotid artery atherosclerosis in hypertensive individuals. This LRP6 variant is associated with lower LRP6 gene expression in atherosclerotic plaques.

Area of Science:

  • Genetics and Molecular Biology
  • Cardiovascular Disease Research
  • Hypertension Studies

Background:

  • Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) variants, including rare (611C) and common (1062V), affect Wnt/ß-catenin signaling.
  • The rare LRP6 variant is linked to hypertension, metabolic issues, and early coronary artery disease.

Purpose of the Study:

  • To determine if the common 1062V LRP6 variant is associated with carotid artery atherosclerosis (CAA) in hypertensive patients.
  • To investigate the relationship between LRP6 genotypes and LRP6 gene expression in carotid plaques.

Main Methods:

  • Retrospective analysis of 334 hypertensive patients (<65 years) undergoing carotid ultrasonography.
  • Evaluation of hypertension, type 2 diabetes, dyslipidemia, glomerular filtration rate, and smoking.
  • Carotid artery atherosclerosis (CAA) defined by atherosclerotic plaques (intima-media thickness ≥ 1.3 mm); logistic regression used.

Main Results:

  • The 1062V LRP6 variant was an independent risk factor for CAA in both unadjusted (OR 2.08) and adjusted (OR 1.92) models (p<0.05).
  • No significant clinical differences between genotypes, except higher fasting glucose in 1062V carriers.
  • LRP6 gene expression was significantly lower in carotid plaques of 1062V carriers (p=0.015).

Conclusions:

  • The 1062V LRP6 variant is strongly associated with CAA in hypertensive patients, independent of other risk factors.
  • LRP6 emerges as a novel candidate gene for atherosclerosis development in the context of hypertension.
Abstract

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