Jul 24, 2012

Diabetes mellitus accelerates cartilaginous metaplasia and calcification in atherosclerotic vessels of LDLr mutant mice

Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology
Ngoc NguyenMei Y Speer

Abstract

Vascular calcification is highly prevalent in patients with type II diabetes mellitus (T2DM). Little is known about whether T2DM is causative. Low-density lipoprotein receptor mutant (LDLr(-/-)) mice were fed with customized diabetogenic and/or procalcific diets to induce atherosclerosis, cartilaginous metaplasia and calcification, along with obesity, hyperglycemia, hyperinsulinemia, and hypercholesterolemia at various levels, and euthanized for study after 18-24 weeks on diet. We found that T2DM accelerated cartilaginous and calcific lesion development by ~3- and 13-fold as determined by incidence of vascular cartilaginous metaplasia and calcification in LDLr(-/-) mice. Lowering dietary fat from ~60% to ~40% kcal reduced body weight and serum glucose and insulin levels, leading to a 2-fold decrease in aortic calcium content. Correlation analysis of calcium content with a calculated insulin resistance index, homeostasis model assessment of insulin resistance, showed a positive correlation of insulin resistance with vascular calcification. Finally, we used genetic fate mapping strategy to trace cells of SM origin in these animals. Vascular smooth muscle cells (SMCs) were found to be a major cell source contributing to osteochond...Continue Reading

Mentioned in this Paper

TAGLN gene
Intima
Collagen Type X
LDLR wt Allele
Diabetes Mellitus, Non-Insulin-Dependent
Tunica Intima
Calcium [EPC]
Arterial System
SOX9 gene
Low Density Lipoprotein Cholesterol Measurement

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