Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction is an early sign of atherosclerosis. Patients with risk factors for atherosclerosis (e.g., hypertension, hyperlipidemia and diabetes mellitus) often show endothelial dysfunction at early stages of atherosclerosis before cardiovascular complications develop. Clinical studies and basic researches are revealing that calcium antagonists not only protect the endothelium through their hypotensive action but also improve the endothelial function through the stimulation of NO production. Regarding the mechanism for this kind of action by nifedipine (a calcium antagonist), it seems likely that the drug stimulates SOD expression in endothelial cells through enhanced VEGF expression by vascular smooth muscle cells, and thus reduces oxidative stress, leading to increased NO production.
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PMID:[Calcium antagonists and endothelial function]. 1619 12

Endothelial dysfunction contributes to mechanisms of atherogenesis and its clinical manifestations, including coronary heart disease. Cardiovascular risk factors have been linked directly to a loss of endothelial function, such as endothelium-dependent nitric oxide (NO) release, resulting in abnormal vasodilation in response to various stimuli. There is evidence that multiple risk factors, including hypertension and hyperlipidemia, lead to a synergistic effect on endothelial dysfunction, likely through oxidative stress mechanisms. Damage to the endothelium leads to reduced NO bioavailability and facilitates vessel wall permeability to low-density lipoprotein. Certain agents, including the antihypertensive drug amlodipine and the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) atorvastatin, are known to influence endothelial function and NO bioavailability directly; these properties may contribute to clinical benefits. Recent experimental evidence at the cellular level indicates that these agents stimulate NO release from human endothelial cells in a highly synergistic fashion. The clinical implications of these observations are discussed in this article in the context of cardiovascular risk factor management strategies.
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PMID:A rationale for combination therapy in risk factor management: a mechanistic perspective. 1635 9

Endothelial dysfunction (ED) is an early feature of cardiovascular risk and diabetes. Hyperglycemia and hyperlipidemia are causative factors. Excessive endothelial mitochondrial superoxide (ROS) production with hyperglycemia and hyperlipidemia is a key mechanism. Inositol components of an insulin inositol glycan mediator, d-chiro-inositol (DCI) and 3-O-methyl DCI (pinitol), decrease hyperglycemia and hyperlipidemia. We tested whether these, myoinositol and dibutyryl DCI (db-DCI), would prevent or reverse ED in diabetic rats and rabbits. Oral inositols reduced hyperglycemia and hypertriglyceridemia with different potencies and prevented ED in rat aortic rings and mesenteric beds. Inositols added in vitro to five diabetic tissues reversed ED. Relaxation by Ach, NO, and electrical field stimulation was potentiated by inositols in vitro in rabbit penile corpus cavernosa. Inositols in vitro restored impaired contraction by the eNOS inhibitor l-NAME and increased NO effectiveness. DCI and db-DCI decreased elevated ROS in endothelial cells in high glucose and db-DCI reduced PKC activation, hexosamine pathway activity, and advanced glycation end products to basal levels. Xanthine/xanthine oxidase generated superoxide was reduced by superoxide dismutase or inositols, with db-DCI efficacious in a mechanism requiring chelated Fe(3+). Histochemical examination of rat aortic rings for protein SNO demonstrated a decrease in diabetic rings with restoration by inositols. In summary, inositols prevented and reversed ED in rat and rabbit vessels, reduced elevated ROS in endothelial cells, potentiated nitrergic or vasculo-myogenic relaxations, and preserved NO signaling. These effects are related to their metabolic actions, direct superoxide scavenging, and enhancing and protecting NO signaling. Of the inositols tested, db-DCI was most effective.
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PMID:Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide. 1637 99

Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity.
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PMID:[Cytokines, endothelial dysfunction, and insulin resistance]. 1676 96

Systemic lupus erythematosus (SLE) is associated with severe and premature cardiovascular disease, which cannot be explained by traditional risk factors alone. This study aims to investigate novel cardiovascular risk factors and cardiac event predictors in inactive SLE female patients who do not have any major cardiovascular risk factors. Twenty-five inactive (SLE disease activity index score <4) SLE female patients and 22 healthy control women were studied. SLE patients with a history of diabetes mellitus, hypertension, hyperlipidemia, smoking, or coronary artery disease (CAD) were excluded. Venous blood samples were analyzed for lipid subfractions and novel cardiovascular risk factors such as lipoprotein (a), homocysteine, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and serum amyloid A (SAA) levels. Endothelial dysfunction was assessed by flow-mediated dilatation (FMD) from the brachial artery at baseline and during reactive hyperemia. SLE patients and controls were similar in terms of age (40+/-10 years vs 38+/-10 years, p = NS). No significant difference was found between the groups regarding family history of premature CAD, blood pressure, body mass index, lipoprotein (a), homocysteine, fibrinogen, SAA, apoprotein A-1 and B levels. Compared with the controls, SLE patients had higher levels of hs-CRP [median (range): 1.82 (0.02-0.98) vs 0.68 (0.02-0.35), p=0.04]. FMD was lower in SLE patients than controls (7.1+/-2.1 vs 11.4+/-1.2%, p<0.001). Increased levels of hs-CRP and decreased FMD were found in inactive SLE patients. Increased hs-CRP levels may reflect ongoing low-grade inflammation that could be a cause of impaired FMD in SLE patients. These findings suggest that SLE patients without traditional major cardiovascular risk factors may have increased risk of cardiovascular disease and future cardiac events.
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PMID:Novel cardiovascular risk factors and cardiac event predictors in female inactive systemic lupus erythematosus patients. 1690 27

Endothelial dysfunction due to the reduced bioavailability of nitric oxide (NO) is involved in the course of atherosclerotic cardiovascular disease as well as chronic kidney disease (CKD). NO is synthesized from L-arginine via the action of NO synthase, which is blocked by endogenous L-arginine analogues such as asymmetric dimethylarginine (ADMA). ADMA is a naturally occurring amino acid found in plasma and various types of tissues. The plasma level of ADMA is reported to be associated with cardiovascular risk factors such as hypertension, diabetes, hyperlipidemia, and CKD, and is a strong predictor for cardiovascular disease and the progression of CKD. In this review, we discuss the biology of ADMA, the molecular mechanisms of the elevation of ADMA levels in CKD, and the pathological role of ADMA in patients with CKD.
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PMID:Asymmetric dimethylarginine (ADMA) is a novel emerging risk factor for cardiovascular disease and the development of renal injury in chronic kidney disease. 1759 10

Erectile dysfunction (ED) is a common condition with a significant effect on quality of life. The prevalence of ED increases with age and other risk factors (hypertension, diabetes, smoking, coronary heart disease, dyslipidemia and depression). Nitric oxide (NO) activity is adversely affected, in penile and vascular tissue, by these risk factors. Endothelial dysfunction and a reduced generation or bioavailability of NO have emerged as major pathophysiological mechanisms in ED. Hyperlipidemia may impair erectile function by affecting endothelial and smooth muscle cells of the penis. Oxidized low-density lipoprotein is a causative factor for the impaired relaxation response of the corpus cavernosum. Elevated serum cholesterol and reduced high density lipoprotein cholesterol levels are associated with an increased risk of ED. It follows that treating dyslipidemia could have a beneficial effect on ED. Phosphodiesterase type 5 inhibitors are now considered as first line treatment for ED. There is evidence that statins improve responses to these drugs. ED is considered as a warning sign of silent or early vascular disease. The use of statins may be beneficial in these patients.
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PMID:Dyslipidemia as a risk factor for erectile dysfunction. 1762 14

Combined hyperlipidemia results from overproduction of hepatically synthesized apolipoprotein B in very low-density lipoproteins in association with reduced lipoprotein lipase activity. Thus, this condition is typically characterized by concurrent elevations in total cholesterol and triglycerides with decreased high-density lipoprotein cholesterol. High levels of apolipoprotein B-containing lipoproteins, most prominently carried by low-density lipoprotein (LDL) particles, are an important risk factor for coronary heart disease. Statin therapy is highly effective at lowering LDL cholesterol. Despite the benefits of statin treatment for lowering total and LDL cholesterol, many statin-treated patients still have initial or recurrent coronary heart disease events. In this regard, combined therapy with statins and fibrates is more effective in controlling atherogenic dyslipidemia in patients with combined hyperlipidemia than either drug alone. Furthermore, statins and fibrates activate PPARalpha in a synergistic manner providing a molecular rationale for combination treatment in coronary heart disease. Endothelial dysfunction associated with cardiovascular diseases may contribute to insulin resistance so that there may also be additional beneficial metabolic effects of combined statin/fibrates therapy. However, there has been little published evidence that combined therapy is synergistic or even better than monotherapy alone in clinical studies. Therefore, there is a great need to study the effects of combination therapy in patients. When statins are combined with gemfibrozil therapy, this is more likely to be accompanied by myopathy. However, this limitation is not observed when fenofibrate, bezafibrate, or ciprofibrate are used in combination therapy.
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PMID:Vascular and metabolic effects of treatment of combined hyperlipidemia: focus on statins and fibrates. 1765 32

Cardiovascular diseases like hypertension, hyperlipidemia, diabetes mellitus and obesity are the important predictors of erectile dysfunction (ED). Endothelial dysfunction is proposed to be the underlying cause of ED, just like coronary artery disease. Sildenafil was originally developed to treat angina pectoris but later on was recognized as novel treatment option for impotence. To date, sildenafil has been the most extensively studied PDE (phosphodiesterase)-5 inhibitor. Currently two more PDE-5 inhibitors, tadalafil and vardenafil, are under study. Newer compounds have certain advantages over sildenafil, including greater selectivity for PDE-5 compared with other isoenzymes, absence of effect of food on absorption, faster onset and longer duration of action. PDE-5 inhibitors are emerging as novel therapeutic tools with a potential to protect or enhance endothelial function in humans and to selectively improve regional blood flow. The FDA has recently approved a reformulation of sildenafil for the treatment of pulmonary arterial hypertension. Raynaud's phenomenon, respiratory disorders with ventilation/ perfusion mismatch, congestive cardiac failure, hypertension and stroke are the other conditions in which PDE-5 inhibitors are being tried. It is hoped that this group of drugs will soon emerge as a novel weapon in the armamentarium against various cardiovascular and pulmonary diseases.
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PMID:Novel phosphodiesterase-5 inhibitors: current indications and future directions. 1817 38

There is increased awareness regarding the close association between cardiovascular disease and erectile dysfunction, especially because both conditions share common risk factors such as diabetes mellitus, hypertension, smoking, hyperlipidemia, and a sedentary lifestyle. Recent studies suggest that erectile dysfunction could be considered a potential marker for underlying silent cardiac or vascular disease processes. Endothelial dysfunction seems to play a major role in both sexual dysfunction and heart disease. With the initiation in 1998 of vasoactive drugs such as the phosphodiesterase-5 inhibitors for the treatment of erectile dysfunction, the underlying vascular components of erectile dysfunction have become a more prominent focus of attention in the clinical and research setting. This review critically examines the background, pathophysiology, and mechanisms behind erectile dysfunction and its close correlation to cardiovascular disease.
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PMID:The relationship between erectile dysfunction and cardiovascular disease. Part I: pathophysiology and mechanisms. 1819 44


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