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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macula densa cells have an important role in the regulation of glomerular blood flow and glomerular filtration by its regulation of afferent arteriolar vascular tone. Nitric oxide derived from neuronal nitric oxide synthase (nNOS) in macula densa can dilate afferent arterioles. Macula densa nNOS is important for renin secretion, and its expression is regulated by dietary salt, renal angiotensin II, intracellular pH, and other factors. In salt-sensitive hypertension, nNOS is suppressed, whereas in SHR or in the early phase of diabetes, nNOS is increased in macula densa along with NADPH oxidase, which limits NO bioavailability. Renal damage induced by hypertension, diabetes, and hyperlipidemia could be prevented by enhancement of nNOS in macula densa with ACEI, dipyridamole, alpha(1)-receptor blocker, a low-salt diet, or sodium bicarbonate. Sodium bicarbonate is a safe and clinically available enhancer of nNOS in macula densa that increases glomerular blood flow and prevents the reduction of GFR in radiocontrast nephropathy and chronic renal failure. In conclusion, the enhancement of nNOS in the macula densa can be a promising strategy to prevent reduction of renal function.
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PMID:Role of macula densa neuronal nitric oxide synthase in renal diseases. 1657 7

Hyperlipidemia and hypertension are frequently observed in patients with coronary artery disease. It has been proposed that an interaction between low-density lipoprotein, especially its oxidized form (ox-LDL), and renin-angiotensin system (RAS) activation is a major determinant of atherogenesis. Ox-LDL accumulation in the blood vessels enhances the expression and activation of RAS components; on the other hand, activation of RAS stimulates the accumulation of LDL and its oxidation into ox-LDL in the blood vessels. Individually ox-LDL and RAS activation induce oxidative stress and inflammatory cascade, whereas their combination exerts a synergistic effect. This concept of cross-talk between ox-LDL/hyperlipidemia and RAS activation has been proven in laboratory animals. Clinical trials also suggest that blockade of hyperlipidemia and RAS may have a synergistic salutary effect on the outcome of patients with hypertension and/or manifestations of atherosclerosis. This concept needs to be evaluated further in large clinical studies.
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PMID:Interaction of oxidized low-density lipoprotein and the renin-angiotensin system in coronary artery disease. 1667 47

Human essential hypertension is due to interacting genetic and environmental factors. Spontaneously hypertensive rats have been genetically selected as models in this setting. The genetically hypertensive rat model that we have selected is the only one to associate mild hypertension with a "metabolic syndrome" (increased body weight, proteinuria and hyperlipidemia and elevated insulin/glucose ratio). This is a renin-dependent model of hypertension, in which low-dose (non antihypertensive) angiotensin-converting-enzyme inhibitor therapy affords significant and durable nephroprotection.
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PMID:[Human essential hypertension and genetic hypertension in rats: the Lyon model]. 1687 49

Eighty percent of coronary deaths occur in people above 65 years of age. Fifty percent of deaths in persons above 85 years of age is due to coronary artery disease. The overall aging of the population and the improvement in survival of patients with coronary artery disease has been creating a growing large population of elderly adults who are elegible for secondary prevention. Multiple clinical trials and research trials have revealed evidence based information confirming the usefulness and effectiveness of secondary prevention of coronary artery disease in the elderly patient. The secondary prevention beneficial results have been obtained by addressing and controlling the predisposing items recognized a coronary risk factors. Secondary preventive measures, including lifestyle modifications and pharmacotherapy, modifying risk factors in elderly patients, have been shown to reduce morbidity and mortality from coronary artery disease. Evidence based data on prevention in elderly patients with coronary artery disease concerning smoking cessation, treatment of hypertension, control of hyperlipidemia, improved dietary patterns, physical activity, moderation in alcohol intake, management of diabetes, weight management, use of antiplatelet agents, beta blockers and renin-angiotensin-andosterone blockers is summarized. Emphasis has been given to AHA/ACC consensus statements on the prevention of coronary artery disease.
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PMID:Evidence based secondary prevention of coronary artery disease in the elderly--2006. 1720 93

A new concept has been proposed to capture the flow of events and chain reactions associated with cardiovascular risk: the metabolic domino. The metabolic domino differs for each individual based on their genetic predisposition. Lifestyle changes are the first dominoes to fall, which lead to obesity and insulin resistance, followed by postprandial hyperglycemia, hypertension, and hyperlipidemia. Atherosclerosis then begins, and diabetes occurs once the domino for impairment of insulin secretion has toppled. Progression of the atherosclerotic process can lead to cardiovascular events such as ischemic heart diseases or cerebrovascular disorders. Preclinical and clinical data indicate that treatments which inhibit the renin angiotensin system, such as angiotensin receptor blockers, can suppress the onset of diabetes and, when administered even earlier in the metabolic domino, reduce the development of hypertension in at-risk individuals. The inhibition of inflammation with thiazolidinedione can also block the sequence of events leading to cardiovascular outcomes, as was shown with pioglitazone in the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive).
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PMID:Metabolic domino: new concept in lifestyle medicine. 1724 76

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. This syndrome is occurring at epidemic rates, with dramatic consequences for human health worldwide, and appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in fructose intake, which appears to be an important causative factor in the metabolic syndrome. There is also experimental and clinical evidence that the amount of magnesium in the western diet is insufficient to meet individual needs and that magnesium deficiency may contribute to insulin resistance. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenic factor in the development of metabolic syndrome. Pro-inflammatory molecules produced by adipose tissue have been implicated in the development of insulin resistance. The present review will discuss experimental evidence showing that the metabolic syndrome, high fructose intake and low magnesium diet may all be linked to the inflammatory response. In many ways, fructose-fed rats display the changes observed in the metabolic syndrome and recent studies indicate that high-fructose feeding is associated with NADPH oxidase and renin-angiotensin activation. The production of reactive oxygen species results in the initiation and development of insulin resistance, hyperlipemia and high blood pressure in this model. In this rat model, a few days of experimental magnesium deficiency produces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, release of inflammatory cytokines, appearance of the acute phase proteins and excessive production of free radicals. Because magnesium acts as a natural calcium antagonist, the molecular basis for the inflammatory response is probably the result of a modulation of the intracellular calcium concentration. Potential mechanisms include the priming of phagocytic cells, the opening of calcium channels, activation of N-methyl-D-aspartate (NMDA) receptors, the activation of nuclear factor-kappaB (NFkB) and activation of the renin-angiotensin system. Since magnesium deficiency has a pro-inflammatory effect, the expected consequence would be an increased risk of developing insulin resistance when magnesium deficiency is combined with a high-fructose diet. Accordingly, magnesium deficiency combined with a high-fructose diet induces insulin resistance, hypertension, dyslipidemia, endothelial activation and prothrombic changes in combination with the upregulation of markers of inflammation and oxidative stress.
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PMID:High fructose consumption combined with low dietary magnesium intake may increase the incidence of the metabolic syndrome by inducing inflammation. 1740 91

Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been recognized as a predominant factor to induce the ischemic retinal neovascularization. We found that retinal vascular cells have a characteristic pattern in VEGF receptor expression, which causes vascular pathology more frequently in the retina than in other organs. Neuropilin 1 (NRP 1), which enhances VEGF receptor function, is abundantly expressed in the retinal endothelial cells and is upregulated by VEGF itself and by hypoxia to regulate a positive feedback mechanism in retinal neovascularization. This receptor could be a unique target for retina-specific therapy. Lifestyle-related diseases increase along with aging and have further increased due to changes in Japanese lifestyle imitating that of Western countries. We found that the renin-angiotensin system which regulates hypertension and cardiovascular diseases, and adipocytokines which are abnormally secreted in obesity, act as proangiogenic factors. Regulation of such lifestyle-related disease factors is important for the treatment of retinal vascular diseases. Finally, we found that erythropoietin is an ischemia-induced angiogenic factor that acts independently and as potently as VEGF in proliferative diabetic retinopathy (PDR). Our study utilizing human vitreous samples demonstrates that the VEGF level is particularly high and strongly associated with angiogenic activity in PDR patients. The potential of VEGF inhibitors has recently been recognized in clinical applications. The manipulation of each angiogenic factor and adipocytokine that we report here could become potential therapy in the near future.
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PMID:[Aging and retinal vascular diseases]. 1740 63

The cardiometabolic syndrome consists of several major components: hypertension, hyperinsulinemia, hyperlipidemia, and hyperglycemia. Central to this syndrome are insulin resistance and generation of reactive oxygen species; these features are particularly prominent in patients with type 2 diabetes mellitus. In this context, large clinical trials have shown that blockade of the renin-angiotensin system (RAS) is protective against type 2 diabetes. In spite of these solid clinical data, the mechanistic pathways by which RAS blockade achieves these protective effects have yet to be resolved. A recently identified local pancreatic islet RAS has, however, been implicated in this regard. Furthermore, RAS blockade was recently shown to enhance islet blood flow, oxygen tension, and insulin biosynthesis, thus improving beta-cell function and glucose tolerance. Meanwhile, RAS activation may also influence islet cell inflammatory responses, apoptosis, fibrosis, and superoxide anion production. This RAS-associated oxidative stress can induce islet cell dysfunction in the pancreas and insulin resistance in peripheral tissues.
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PMID:Involvement of the pancreatic renin-angiotensin system in insulin resistance and the metabolic syndrome. 1767 33

The metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular diseases and diabetes mellitus. There is widespread agreement that the renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of insulin resistance and cardiovascular disease in diabetes. Indeed, large clinical trials have demonstrated substantial benefit of the blockade of this system for cardiovascular end-organ protection. Thus the blockade of the RAS may be a promising strategy for the treatment of the patients with the metabolic syndrome. Although several types of angiotensin II type 1 (AT(1)) receptor blockers (ARBs) are commercially available for the treatment of patients with hypertension, we have recently found that telmisartan (Micardis) could have the strongest binding affinity to AT(1) receptor. Further, telmisartan is reported to act as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). These observations suggest that, due to its unique PPAR-gamma-modulating activity, telmisartan may be one of the most promising sartans for the treatment of cardiometabolic disorders. In this paper, we reviewed the potential utility of telmisartan in insulin resistance and vascular complications in diabetes.
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PMID:Potential utility of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity for the treatment of cardiometabolic disorders. 1769 61

Previous studies of hospitalized patients have suggested an "obesity paradox" with lower short-term mortality as weight increases. We hypothesized that some of this difference might be related to more aggressive management. To evaluate the effect of body mass index (BMI) on treatments and outcomes in patients with coronary artery disease (CAD), the Get With The Guidelines database was investigated. From 409 United States hospitals, 130,139 hospitalizations for CAD were identified with documented height and weight. Patients were stratified by BMI, with 3,305 (2.5%) underweight (BMI <18.5 kg/m(2)), 34,697 (27%) of healthy weight (BMI 18.5 to 24.9 kg/m(2)), 47,883 (37%) overweight (BMI 25 to 29.9 kg/m(2)), 37,686 (29%) obese (BMI 30 to 39.9 kg/m(2)), and 6,568 (5%) extremely obese (BMI > or =40 kg/m(2)). As BMI increased, patients were significantly younger but more likely to be men and have hypertension, diabetes, and hyperlipidemia. Unadjusted in-hospital mortality was highest in the underweight group (10.4%) and significantly lower in the healthy-weight (5.4%), overweight (3.1%), obese (2.4%), and extremely obese (2.9%) patients. Higher BMI was associated with increased use of standard medical therapies such as aspirin, beta blockers, inhibitors of the renin-angiotensin system, and lipid-lowering therapy in the hospital and at discharge. In adjusted analyses, compared with the healthy-weight group, overweight and obese patients were more likely to undergo invasive procedures and had lower mortality (p <0.01 for all odds ratios). In conclusion, increasing BMI appears to be associated with better use of guideline-recommended medical treatment and invasive management of CAD, which may explain the observed lower rates of in-hospital mortality.
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PMID:Medical therapies and invasive treatments for coronary artery disease by body mass: the "obesity paradox" in the Get With The Guidelines database. 1795 Jul 85


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