Increased Atherosclerotic Lesion Calcification in a Novel Mouse Model Combining Insulin Resistance, Hyperglycemia, and Hypercholesterolemia

Abstract

Abstract-No mouse model is currently available where the induction of type 2 diabetes on an atherosclerotic background could be achieved without significant concomitant changes in plasma lipid levels. We crossbred 2 genetically modified mouse strains to achieve a model expressing both atherosclerosis and characteristics of type 2 diabetes. For atherosclerotic background we used low-density lipoprotein receptor-deficient mice synthetizing only apolipoprotein B100 (LDLR Ϫ/Ϫ

Plasma osteoprotegerin levels predict cardiovascular and all-cause mortality and deterioration of kidney function in type 1 diabetic patients with nephropathy

“…In addition, osteoprotegerin may be related to the development of medial calcification, which is frequently present in patients with diabetes [34,35]. Two recent experimental studies have confirmed the finding of increased expression of the gene encoding osteoprotegerin and production of the protein in arteries from animals with experimental diabetes [10,11]. At a first glance, it may seem contradictory that osteoprotegerin-a putative beneficial calcification inhibitor-accumulates in the arterial system in diabetes and that a high concentration of plasma osteoprotegerin is a cardiovascular risk marker.…”

“…However, the exact functions of osteoprotegerin in relation to vascular calcifications and other arterial functions are not yet well defined [6][7][8][9]. Interestingly, we have previously observed that osteoprotegerin accumulates in human aortic tissue from patients with type 1 and type 2 diabetes, a finding that has very recently been confirmed in studies of experimental models of diabetic arteriopathy [10,11].…”

Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models

“…In this regard, other effects of diabetes on plaque composition were not measured and cannot be excluded. For instance, increased mineralization of blood vessels is a hallmark of insulin resistance/diabetes in both humans and animal models (12).…”

Shift of Macrophage Phenotype Due to Cartilage Oligomeric Matrix Protein Deficiency Drives Atherosclerotic Calcification

“…After bone marrow transplantation, chimeric mice were first genotyped to validate the success of transplantation (Online Figure IV) and then were fed with a Western-type diet for 16 weeks to accelerate the formation of atherosclerotic calcification. 30 There were no differences among the mice fed the Western-type diet in body weight, blood pressure, blood cell profile, serum lipids, and biochemical indexes, including phosphate, calcium, blood urea nitrogen, and creatinine (Online Table III (Figure 2B and 2C). Similar results were obtained by the use of von Kossa staining to quantify the atherosclerotic calcification in chimeric mice (Figure 2A and 2E Figure 2D).…”