glucuronyl-glucosamine-glycan-sulfate and Dyslipidemias

Diabetic nephropathy is one of the main causes of end-stage renal disease (ESRD) and is associated with elevated cardiovascular morbidity and mortality.. Current renoprotective treatments for diabetic nephropathy include strict glycemic and optimal blood pressure control, proteinuria/albuminuria reduction and the use of renin-angiotensin-aldosterone system (RAAS) blocking agents. However, the renoprotection provided by these treatments is only partial, calling for more effective approaches.. This review examines emerging strategies for the treatment of diabetic nephropathy, including aggressive RAAS blockade, statins, glitazones, ruboxistaurin, and other promising agents.. In diabetic patients with overt nephropathy, multipharmacological interventions represent a promising way to prevent progression to ESRD. Results of ongoing trials are needed to establish whether the current standard of care of diabetic nephropathy might be improved with these new strategies.

Topics: Aldehyde Reductase; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal; Diabetic Nephropathies; Drugs, Investigational; Dyslipidemias; Endothelin Receptor Antagonists; Glycosaminoglycans; Humans; Hypertension; Hypoglycemic Agents; Mineralocorticoid Receptor Antagonists; Protein Kinase C; Renin

Patients with HIV are at an increased risk of cardiovascular disease. In this study we investigated the effect of Nef, a secreted HIV protein responsible for the impairment of cholesterol efflux, on the development of atherosclerosis in two animal models. ApoE(-/-) mice fed a high-fat diet and C57BL/6 mice fed a high-fat, high-cholesterol diet were injected with recombinant Nef (40 ng/injection) or vehicle, and the effects of Nef on development of atherosclerosis, inflammation, and dyslipidemia were assessed. In apoE(-/-) mice, Nef significantly increased the size of atherosclerotic lesions and caused vessel remodeling. Nef caused elevation of total cholesterol and triglyceride levels in the plasma while reducing high-density lipoprotein cholesterol levels. These changes were accompanied by a reduction of ABCA1 abundance in the liver, but not in the vessels. In C57BL/6 mice, Nef caused a significant number of lipid-laden macrophages presented in adventitia of the vessels; these cells were absent from the vessels of control mice. Nef caused sharp elevations of plasma triglyceride levels and body weight. Taken together, our findings suggest that Nef causes dyslipidemia and accumulation of cholesterol in macrophages within the vessel wall, supporting the role of Nef in pathogenesis of atherosclerosis in HIV-infected patients.-Cui, H. L., Ditiatkovski, M., Kesani, R., Bobryshev, Y. V., Liu, Y., Geyer, M., Mukhamedova, N., Bukrinsky, M., Sviridov, D. HIV protein Nef causes dyslipidemia and formation of foam cells in mouse models of atherosclerosis.

Topics: Animals; Apolipoproteins E; Atherosclerosis; ATP Binding Cassette Transporter 1; Cholesterol; Dyslipidemias; Foam Cells; Glycosaminoglycans; HIV; HIV Infections; Human Immunodeficiency Virus Proteins; Inflammation; Lipoproteins, HDL; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; nef Gene Products, Human Immunodeficiency Virus; Triglycerides