Rosuvastatin increases vascular endothelial PPARgamma expression and corrects blood pressure variability in obese dyslipidaemic mice.

Aims: Statins improve atherosclerotic diseases through cholesterol-reducing effects. Whether the latter exclusively mediate similar benefits, e.g.

Dyslipidaemia in type II diabetic mice does not aggravate contractile impairment but increases ventricular stiffness.

Aims: Type II diabetes, often associated with abdominal obesity, frequently leads to heart failure. Clinical and epidemiological evidence suggests that supplemental dyslipidaemia and hypertension, as clustered in the metabolic syndrome, aggravate the cardiovascular outcome. The differential impact of type II diabetes and the metabolic syndrome on left ventricular function, however, remains incompletely defined.

Defective leptin/leptin receptor signaling improves regulatory T cell immune response and protects mice from atherosclerosis.

Objective: Obesity is a major risk factor for atherosclerosis and is associated with increased cardiovascular morbidity and mortality. However, the precise molecular pathways responsible for this close association remain poorly understood.

Methods And Results: In this study, we report that leptin-deficiency (ob/ob) in low-density lipoprotein receptor knockout (ldlr(-/-)) mice induces an unexpected 2.

Human paraoxonase-1 overexpression inhibits atherosclerosis in a mouse model of metabolic syndrome.

Background: The metabolic syndrome is typified by obesity, dyslipidemia, diabetes, hypertension, increased oxidative stress, and accelerated atherosclerosis. Paraoxonase1 (PON1), a high-density lipoprotein (HDL)-associated antioxidant enzyme that prevents the oxidation of low-density lipoprotein (LDL), is low in the metabolic syndrome.

Methods And Results: We used adenovirus-mediated PON1 gene transfer (AdPON1) to overexpress human PON1 in mice with combined leptin and LDL receptor deficiency, a model of metabolic syndrome.

Peroxisome proliferator-activated receptor-alpha,gamma-agonist improves insulin sensitivity and prevents loss of left ventricular function in obese dyslipidemic mice.

Objective: We investigated the effect of a dual peroxisome proliferator-activated receptor (PPAR)alpha,gamma-agonist on atherosclerosis and cardiac function in mice with combined leptin and low-density lipoprotein receptor deficiency (DKO). In these mice, obesity, diabetes, and hyperlipidemia are associated with accelerated atherosclerosis and loss of cardiac function.

Methods And Results: We treated 12-week-old DKO mice with the PPARalpha,gamma-agonist (S)-3-(4-(2-carbazol-9-yl-ethoxy) phenyl-2-ethoxy-propionic-acid) for 12 weeks.

Weight-loss-associated induction of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma correlate with reduced atherosclerosis and improved cardiovascular function in obese insulin-resistant mice.

Background: Weight loss in obese insulin-resistant but not in insulin-sensitive persons reduces coronary heart disease risk. To what extent changes in gene expression are related to atherosclerosis and cardiovascular function is unknown.

Methods And Results: We studied the effect of diet restriction-induced weight loss on gene expression in the adipose tissue, the heart, and the aortic arch and on atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency.

Increased low-density lipoprotein oxidation and impaired high-density lipoprotein antioxidant defense are associated with increased macrophage homing and atherosclerosis in dyslipidemic obese mice: LCAT gene transfer decreases atherosclerosis.

Background: Obesity-associated dyslipidemia in humans is associated with increased low-density lipoprotein (LDL) oxidation. Mice with combined leptin and LDL receptor deficiency are obese and show severe dyslipidemia and insulin resistance. We investigated the association between oxidation of apolipoprotein B-containing lipoproteins, high-density lipoprotein (HDL) antioxidant defense, and atherosclerosis in these mice.