Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic renal disease is accompanied by characteristic abnormalities of lipid metabolism, which appear as a consequence of nephrotic syndrome or renal insufficiency and are reflected in an altered apolipoprotein profile as well as elevated plasma lipid levels. Experimental and clinical studies have suggested a correlation between the progression of renal disease and dyslipidemia. High cholesterol and triglyceride plasma levels have been demonstrated to be independent risk factors for progression of renal disease in humans. The underlying pathophysiologic mechanisms for the relationship between lipid levels and progression of renal disease are not yet fully understood, although there are data that oxidative stress and insulin resistance may mediate the lipid-induced renal damage. In the animal model, lipid-lowering agents seem to ameliorate glomerular damage, preventing glomerulosclerosis and interstitial fibrosis. Although evidence from clinical studies indicates that statin therapy is associated with significant benefit in individuals with established chronic renal failure, whether lipid reduction can slow the renal functional decline awaits a primary renal outcome lipid-lowering therapy study.
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PMID:Lipids and renal disease. 1656 40

Metabolic syndrome is associated with dyslipidemia, which is thought to contribute in part to the development of chronic kidney disease (CKD). This review discusses the factors that regulate intracellular handling of lipids and their relationship to disordered mesangial cell function. Specific attention is paid to those factors such as fatty acid translocase/scavenger receptor BII, proliferator-activated receptor delta, insulin-like growth factor-1, inflammation and hypertriglyceridemia that are altered in the metabolic syndrome. CKD also causes an increase in triglycerides and a decrease in high-density lipoprotein that mimic the lipid abnormalities of metabolic syndrome, which accelerate the progression of CKD and increase the risk for cardiovascular mortality. There is a special emphasis on foam cells in the kidney and lipid-mediated changes in intrinsic kidney cells that lead to glomerulosclerosis and interstitial fibrosis. Correlates to whole animal and humans studies are included.
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PMID:Lipid metabolism and renal disease. 1692 36

Fasudil, a Rho-kinase inhibitor, may improve insulin signaling. However, its long-term effect on metabolic abnormalities and its preventive effect on diabetic nephropathy are still unknown. We assessed these effects of fasudil in insulin-resistant diabetic rats, comparing them with those of an angiotensin II receptor blocker, olmesartan. Male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka, non-diabetic control, rats at 15 weeks of age were used. OLETF rats were randomized to receive a low or a high dose of fasudil or olmesartan for 25 weeks. To examine the therapeutic effects after the development of diabetes, OLETF rats at 30 weeks of age were given fasudil for 10 weeks. Administration of high-dose fasudil completely suppressed the development of diabetes, obesity, and dyslipidemia and increased serum adiponectin levels in OLETF rats. High-dose olmesartan also decreased hemoglobin A1c and increased serum adiponectin. There was a significant correlation between hemoglobin A1c and serum adiponectin or free fatty acid levels. The treatment with high-dose fasudil ameliorated proteinuria, glomerulosclerosis, renal interstitial fibrosis, and macrophage infiltration in OLETF rats. Olmesartan, even at the low dose, suppressed renal complications. The treatment with fasudil after the development of diabetes improved the metabolic abnormalities in OLETF rats, but could not suppress the progression of nephropathy. We conclude that the long-term treatment with fasudil prevents the development of diabetes, at least in part, by improving adipocyte differentiation in insulin-resistant diabetic rats. Early use of fasudil may prevent diabetic nephropathy.
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PMID:A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats. 1733 27

In diabetic and nondiabetic chronic nephropathies, high blood pressure and urinary loss of proteins represent major determinants of progressive renal function decline. Reducing blood pressure with drugs that inhibit the renin-angiotensin system also lowers glomerular hypertension and ameliorates glomerular sieving properties, thus reducing proteinuria. Reducing urinary protein levels with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARA) limits renal function decline to the point that remission of disease and regression of renal lesions have been observed in experimental animals and in humans. This therapy, however, may not be effective in all patients. For patients who do not achieve complete remission of proteinuria, renoprotective treatment should include intensified blood pressure control (and metabolic control in diabetes) and amelioration of dyslipidemia. Early intervention, before progressive glomerulosclerosis and scarring is initiated by increased protein traffic, may be important to maximize reno- and cardioprotection, especially in diabetes.
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PMID:Does remission of renal disease associated with antihypertensive treatment exist? 1744 29

Chronic kidney disease (CKD) occurs in all age groups, including children. Regardless of the underlying cause, CKD is characterized by progressive scarring that ultimately affects all structures of the kidney. The relentless progression of CKD is postulated to result from a self-perpetuating vicious cycle of fibrosis activated after initial injury. We will review possible mechanisms of progressive renal damage, including systemic and glomerular hypertension, various cytokines and growth factors, with special emphasis on the renin-angiotensin-aldosterone system (RAAS), podocyte loss, dyslipidemia and proteinuria. We will also discuss possible specific mechanisms of tubulointerstitial fibrosis that are not dependent on glomerulosclerosis, and possible underlying predispositions for CKD, such as genetic factors and low nephron number.
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PMID:Mechanisms of progression of chronic kidney disease. 1764 26

The metabolic syndrome (MetS) is defined by a set of metabolic risk factors, including insulin resistance, central obesity, dyslipidemia, hyperglycemia, and hypertension for type 2 diabetes and cardiovascular disease. Although both retrospective and prospective clinical studies have revealed that MetS is associated with chronic renal disease, even with a nondiabetic cause, the cellular and molecular mechanisms in this association remain largely uncharacterized. Recently, increasing evidence suggests that peroxisome proliferator-activated receptors (PPARs), a subgroup of the nuclear hormone receptor superfamily of ligand-activated transcription factors, may play an important role in the pathogenesis of MetS. All three members of the PPAR nuclear receptor subfamily, PPARalpha, -beta/delta, and -gamma, are critical in regulating insulin sensitivity, adipogenesis, lipid metabolism, inflammation, and blood pressure. PPARs have also been implicated in many renal pathophysiological conditions, including diabetic nephropathy and glomerulosclerosis. Ligands for PPARs such as hypolipidemic PPARalpha activators, and antidiabetic thiazolidinedione PPARgamma agonists affect not only diverse aspects of MetS but also renal disease progression. Emerging data suggest that PPARs may be potential therapeutic targets for MetS and its related renal complications. This review focuses on current knowledge of the role of PPARs in MetS and discusses the potential therapeutic utility of PPAR modulators in the treatment of kidney diseases associated with MetS.
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PMID:PPARs and the kidney in metabolic syndrome. 1823 57

The purpose of this study was to evaluate whether the spontaneously hypertensive rat SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP fatty) is a useful animal model to clarify molecular mechanisms that underlie metabolic syndrome. We investigated histopathologic changes in the cardiovascular organs and metabolic characteristics of SHRSP fatty rats, which are congenic rats from a cross between SHRSP and Zucker fatty (ZF) rats. The aortic wall and cardiac, carotid, and renal arteries from SHRSP and SHRSP fatty rats were thicker than those of ZF rats. The renal cortex in SHRSP and SHRSP fatty rats showed severe glomerulosclerosis. Pancreatic islands in SHRSP fatty and ZF rats showed marked hyperplasia. Steady-state plasma glucose concentrations were higher in SHRSP fatty than in ZF rats. Non-fasting triglyceride levels in SHRSP fatty rats were higher than in ZF rats. DNA synthesis in cultured vascular smooth muscle cells (VSMCs) from SHRSP fatty and SHRSP rats was significantly higher than that in VSMCs from Wistar-Kyoto (WKY) or ZF rats. Levels of platelet-derived growth factor A-chain and transforming growth factor-beta1 mRNAs were higher in VSMCs from SHRSP fatty and SHRSP than from ZF rats. Microarray analysis identified five genes that were significantly upregulated and four genes that were significantly downregulated in visceral adipose tissue of SHRSP fatty rats compared with levels in control strains (SHRSP and ZF rats). These findings suggest that the combination of hypertension and obesity accelerates vascular remodeling, dyslipidemia, and insulin resistance in metabolic syndrome. The phenotype of SHRSP fatty is similar to that of human metabolic syndrome, and therefore, studies of these rats may help clarify the molecular mechanisms that underlie metabolic syndrome in humans.
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PMID:Cardiovascular remodeling and metabolic abnormalities in SHRSP.Z-Lepr(fa)/IzmDmcr rats as a new model of metabolic syndrome. 1871 58

Epidemiological investigations reveal that we must expect a rapid increase in cases of diabetes mellitus in the next few years. As a result, vascular complications in the form of macro- and microangiopathy are also expected to arise more frequently. A classical example of macroangiopathy is coronary arteriosclerosis, microangiopathy is exemplified by diabetic nephropathy. In patients suffering from diabetes, macroangiopathy manifests as atherosclerosis like in nondiabetic patients, characterized by formation of plaques that follows in stages but with an accelerated course due to the different risk factors, especially hyper- and dyslipidemia, with cumulative effects. Thus, atherosclerosis in diabetes begins earlier, is more markedly pronounced and progresses more rapidly. The pathogenetic concept is based on an endothelial lesion that occurs as a result of a diabetes-specific, endothelium-damaging parameters. In case of diabetic microangiopathy histologically characterized by a progressive glomerulosclerosis, arteriolosclerosis and interstitial fibrosis hyperglycemia, along with its consecutive and complex processes that induce matrix increase, is considered to be the primary pathogenetically relevant factor involved. Insulin resistance seems to be the major common denominator at the center of both diabetic macroangiopathy and microangiopathy.
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PMID:Pathogenesis of diabetic macro- and microangiopathy. 1879 42

Metabolic syndrome (MS) encompasses a series of diseases which, when combined, increase vascular risk more than the sum of their individual risks. Insulin resistance (IR) is one of the basic components of MS. - Abdominal fat distribution is an IR marker and is associated to factors increasing vascular risk such as dyslipidemia, high blood pressure, and hyperglycemia, components of the so-called metabolic syndrome. - IR is related to glomerular sclerosis and renal failure through several mechanisms, Including genetic and environmental factors, and stimulation of the renin-angiotensin-aldosterone system. - IR usually precedes development of DM, and therefore contributes to its early identification. MS increases the risk of chronic complications from DM and is associated to an increased prevalence of cardiovascular disease, particularly coronary heart disease, increasing mortality from this cause. - The presence of MS in DM2 is usually associated to a greater prevalence of microalbuminuria or proteinuria and peripheral polyneuropathy.
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PMID:[Metabolic syndrome and kidney disease]. 1901 36

Significant reduction of renal mass causes progressive deterioration of renal function and structure which is mediated by systemic and glomerular hypertension, hyperfiltration, oxidative stress, inflammation, and dyslipidemia. Niacin is known to improve lipid metabolism and exert antioxidant/anti-inflammatory actions. Therefore, we considered that niacin supplementation may attenuate oxidative stress, inflammation, and tissue injury in the remnant kidney. To this end, 56 nephrectomized [chronic kidney disease (CKD)] rats were randomly assigned to niacin-treated (50 mg x kg(-1) x day(-1) in the drinking water for 12 wk) and untreated groups. Sham-operated rats served as controls. The untreated CKD rats exhibited azotemia, hypertension, hypertriglyceridemia, proteinuria, glomerulosclerosis, tubulointerstitial damage, upregulation of MCP-1, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor (TGF)-beta, cyclooxygenase (COX)-1, COX-2, and NAD(P)H oxidase (NOX-4, gp91(phox), p47(phox) and p22(phox) subunits) and activation of NF-kappaB (IkappaB phosphorylation). Niacin administration reduced MCP-1, PAI-1, TGF-beta, p47(phox), p22(phox), COX-1, and NF-kappaB activation, ameliorated hypertension, proteinuria, glomerulosclerosis, and tubulointerstitial injury. Although niacin lowered serum creatinine and raised creatinine clearance, the differences did not reach statistical significance. Thus niacin supplementation helps to attenuate histological injury and mitigate upregulation of oxidative and inflammatory systems in the remnant kidney.
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PMID:Niacin ameliorates oxidative stress, inflammation, proteinuria, and hypertension in rats with chronic renal failure. 1942 Jan 10


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