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)

The process of aging is accompanied by several modifications in the hemostatic system at different levels (blood coagulation, fibrinolysis, platelet activity, vascular endothelium). These changes may explain the higher incidence of arterial and venous thrombosis in the elderly compared to young people. Genetic and environmental factors modulate in different combinations the expression of proteins involved in the hemostatic process. Among the latter, diet and smoking habits play an important role, as well as physical exercise and, for women, hormonal status. A gradual and progressive development of a low-grade inflammatory state (clearly demonstrated in the elderly) is also an important factor that influences hemostasis during aging. In spite of the fact that the increased hypercoagulable state observed with aging may account for the higher incidence of thrombosis in the elderly, the finding of a similar pattern of coagulation activation in healthy centenarians suggests that a hypercoagulable state is compatible with health and longevity. Taking also into consideration that no laboratory parameters of hemostasis are predictive of thrombosis on an individual basis, a physician's behavior towards aging patients (e.g. prescription of hormonal replacement therapy to a woman during menopause) should not be affected by laboratory tests, but mainly by a patient's clinical history and the presence of strong risk factors for thrombosis other than age (e.g. diabetes mellitus, arterial hypertension, dyslipidemia, obesity, smoking).
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PMID:The hemostatic system through aging and menopause. 1981 Dec 41

Insulinoresistance (IR) and endothelial dysfunction (ED) take part in forming cardiovascular complications. Hyperglycemia, dyslipidemia, and compensatory hyperinsulinemia are triggering factors in the development of ED in diabetes mellitus. Hyperactivation of the renin--angiotensin--aldosterone system and increasing influence of the sympathoadrenal system play an important role in the appearance of ED, which is characterized by a decrease in the synthesis of nitric oxide and an increase in the production of vasoconstrictors. At present, drugs used for ED correction only indirectly influence the functioning of endothelial cells. Eight pharmacological groups including more than 30 drugs are reviewed, which are capable of improving the endothelial function. Progress in the pharmacotherapy of ED stimulates the development of approaches to the individual choice of drugs and the directed correction of the functional state of vascular endothelium.
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PMID:[Endothelial dysfunction in diabetes mellitus and possible ways of pharmacological correction]. 2036 1

The endothelial glycocalyx (EG) is an extracellular matrix (ECM) coating the luminal surface of the vascular endothelium. Hyaluronan (HA), a glycosaminoglycan, is an important constituent of the EG that regulates inflammation and repair. By providing a direct link between the endothelium and its ECM, HA contributes to maintaining glycocalyx integrity; emerging evidence indicates a close association between EG deterioration, concomitant loss of HA and the onset of endothelial dysfunction, a phenomenon that is involved in many disorders, including atherosclerosis, diabetes, hypertension and dyslipidemia. This review provides an overview of glycocalyx modification by pathological stimuli and considers the potential of the pharmacological targeting of HA synthesis and binding to limit endothelial dysfunction and to improve vasculoprotection.
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PMID:Targeting hyaluronan of the endothelial glycocalyx for therapeutic intervention. 2073 Jun 94

Statins are believed to exert beneficial effects against cardiovascular disease beyond correction of dyslipidemia. There are however still very sparse data on how individual statins interact with the production of vasoactive eicosanoids and nitric oxide (NO) in human vascular endothelial cells. Here we have determined how fluvastatin affects the mRNA expression of genes associated with vascular reactivity as well as the formation of two major vasodilators, prostacyclin (PGI2) and NO, in human endothelial cells. Also, the influence of fluvastatin on arterial resistance was assessed in isolated small arteries. We show that the promoter activity of prostacyclin synthase (PTGIS), the mRNA expression of PTGIS and endothelial nitric oxide synthase (eNOS), and the production of PGI2 and NO are significantly induced by fluvastatin. Also, strong rapid dilatation ex vivo was observed, with the equal contribution of PGI2 and NO. Our findings in cell culture experiments and in isolated human arteries indicate that fluvastatin-evoked endothelium-derived vasodilator production may confer protection of the endothelial cells via both acute and long-term effects of fluvastatin treatment. If these effects take place in vivo, we suggest a protective pleiotropic role of fluvastatin on the cardiovascular system, particularly at the level of the vascular endothelium, to ameliorate the process of atherogenesis and in the acute manner to reduce vascular tone.
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PMID:Beneficial vasoactive endothelial effects of fluvastatin: focus on prostacyclin and nitric oxide. 2121 9

Homocysteine, a sulfur-containing amino acid formed during the metabolism of methionine, exert cytotoxic effects on vascular endothelium. Molecular mechanisms of homocysteine-induced cellular dysfunction include increased inflammatory cytokine expression, altered nitric oxide bioavailability, induction of oxidative stress, activation of apoptosis and defective methylation. Hyperhomocysteinemia is associated with an increased risk of atherosclerotic and thromboembolic disorders, as well as hyperinsulinemia and may partially account for increased risk of cardiovascular disease associated with insulin resistance. Women with PCOS are more likely to develop components of the metabolic syndrome such as disturbances of carbohydrate metabolism, obesity, hypertension and dyslipidemia, which in turn are risk factors for cardiovascular disease. A number of studies confirmed the presence of increased serum homocysteine concentration in PCOS patients and the possible determinants of this observation are still debated. PCOS treatment options can influence homocysteine levels.
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PMID:Homocysteine metabolism in polycystic ovary syndrome. 2179 5

Statins are widely used in the treatment of dyslipidemia and associated cardiovascular abnormalities including atherosclerosis, hypertension and coronary heart disease. Needless to mention, statins have cholesterol-lowering effects by means of inhibiting 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, a rate-limiting enzyme of cholesterol biosynthesis. Besides cholesterol-lowering effects, statins possess pleiotropic anti-inflammatory, anti-oxidant, anti-platelet and anti-fibrotic properties, which may additionally play imperative roles in statins-mediated cardiovascular protection. However, the precise mechanisms involved in the cardiovascular defensive potential of statins have not completely been elucidated. Intriguingly, a considerable number of studies demonstrated the potential modulatory role of statins on endothelial nitric oxide synthase (eNOS), a key enzyme involved in the regulation of cardiovascular function by generating endothelium-derived relaxing factor (often represented 'nitric oxide'). Worthy of note is that vascular generation of nitric oxide has beneficial anti-inflammatory, anti-platelet and vasodilatory actions. The upregulation of eNOS by statins is mediated through inhibition of synthesis of isoprenoids and subsequent prevention of isoprenylation of small GTPase Rho, whereas statin-induced activation of eNOS is mediated through activation of phosphotidylinositol-3-kinase (PI3K)/protein kinase B (PKB/Akt) signals. Additionally, statins enhance eNOS activation by abrogating caveolin-1 expression in vascular endothelium. In light of this view-point, we suggest in this review that eNOS upregulation and activation, in part, could play a fundamental role in the cardiovascular defensive potential of statins. The eNOS modulatory role of statins may have an imperative influence on the functional regulation of cardiovascular system and may offer new perspectives for the better use of statins in ameliorating cardiovascular disorders.
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PMID:Is targeting eNOS a key mechanistic insight of cardiovascular defensive potentials of statins? 2196 28

The regulation of vascular tone, vascular permeability, and thromboresistance is essential to maintain blood circulation and therefore tissue environments under physiological conditions. Atherogenic stimuli, including diabetes, dyslipidemia, and oxidative stress, induce vascular dysfunction, leading to atherosclerosis, which is a key pathological basis for cardiovascular diseases such as ischemic heart disease and stroke. We have proposed a novel concept termed "vascular failure" to comprehensively recognize the vascular dysfunction that contributes to the development of cardiovascular diseases. Vascular endothelial cells form the vascular endothelium as a monolayer that covers the vascular lumen and serves as an interface between circulating blood and immune cells. Endothelial cells regulate vascular function in collaboration with smooth muscle cells. Endothelial dysfunction under pathophysiological conditions contributes to the development of vascular dysfunction. Here, we address the barrier function and microtubule function of endothelial cells. Endothelial barrier function, mediated by cell-to-cell junctions between endothelial cells, is regulated by small GTPases and kinases. Microtubule function, regulated by the acetylation of tubulin, a component of the microtubules, is a target of atherogenic stimuli. The elucidation of the molecular mechanisms of endothelial dysfunction as a cellular mechanism for vascular failure could provide novel therapeutic targets of cardiovascular diseases.
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PMID:Endothelial dysfunction as a cellular mechanism for vascular failure. 2208 98

The burden of cardiovascular disease (CVD) is increasing worldwide. The increase in the burden is a major concern in developing countries like India. It is well-established that hypertension and dyslipidemia are the two major contributing risk factors for CVD. Various epidemiological studies have shown the prevalence of the co-existence of hypertension and dyslipidemia, in the range of 15 to 31%. The co-existence of the two risk factors has more than an additive adverse impact on the vascular endothelium, which results in enhanced atherosclerosis, leading to CVD. This review emphasizes on the 'co-existence and interplay of dyslipidemia and hypertension'. The authors have termed the co-existence as, 'LIPITENSION'. The term LIPITENSION may help clinicians in easy identification and aggressive management of the two conditions together, ultimately preventing future cardiovascular events.
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PMID:LIPITENSION: Interplay between dyslipidemia and hypertension. 2247 Aug 61

Endothelial dysfunction associated with diabetes and cardiovascular disease is characterized by changes in vasoregulation, enhanced generation of reactive oxygen intermediates, inflammatory activation, and altered barrier function. These endothelial alterations contribute to excess cardiovascular disease in diabetes, but may also play a role in the pathogenesis of diabetes, especially type 2. The mechanisms underlying endothelial dysfunction in diabetes differ between type 1 (T1D) and type 2 diabetes (T2D): hyperglycemia contributes to endothelial dysfunction in all individuals with diabetes, whereas the causative mechanisms in T2D also include impaired insulin signaling in endothelial cells, dyslipidemia and altered secretion of bioactive substances (adipokines) by adipose tissue. The close association of so-called perivascular adipose tissue with arteries and arterioles facilitates the exposure of vascular endothelium to adipokines, particularly if inflammation activates the adipose tissue. Glucose and adipokines activate specific intracellular signaling pathways in endothelium, which in concert result in endothelial dysfunction in diabetes. Here, we review the characteristics of endothelial dysfunction in diabetes, the causative mechanisms involved and the role of endothelial dysfunction(s) in the pathogenesis of T2D. Finally, we will discuss the therapeutic potential of endothelial dysfunction in T2D.
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PMID:Endothelial dysfunction in (pre)diabetes: characteristics, causative mechanisms and pathogenic role in type 2 diabetes. 2341 60

Pathological conditions states such as stroke, diabetes mellitus, hypertension, dyslipidemia are associated with increased levels of free radicals that alter normal function of the vascular endothelium and perturb vascular homeostasis. The redox couples reduced glutathione (GSH)/oxidized glutathione (GSSG), NADH/NAD+, and NADPH/NADP+ play major functions in the intracellular redox balance. Any decrease in tissue or systemic GSH levels under the aforementioned pathologies would enhance oxidative damage to the vascular endothelium. Beside their role as coenzyme that participate in cellular metabolism, pyridine nucleotides serve also as substrate for enzymes involved in DNA repair and longevity. There is scant data on NAD+/NADH kinetics and distribution during human cells proliferation. Here, we determined the influence of cellular GSH status on the early dynamics of nuclear-to-cytosol (N-to-C) NAD+ and nuclear NADH kinetics (6 h interval) over 72 h of endothelial cell proliferation. The IHEC cell line was used as a surrogate for human brain micro vascular endothelial cells. Inhibition of GSH synthesis by buthionine sulfoximine (BSO) and sustained low cellular GSH significantly increased nuclear NADH levels (p<0.01), which correlated with lower nuclear GSH and prolonged cell cycle S-phase. When BSO was removed the pattern of nuclear NAD+ resembled that of control group, but nuclear NADH concentrations remained elevated, as in GSH deficient cells (p<0.01). The coincidence of high nuclear NADH and lower nuclear NAD+ with S-phase prolongation are suggestive of CtBP and NAD+-dependent DNA repair enzyme activation under conditions of decreased cellular GSH. These results provide important insights into GSH control of vascular endothelial growth and restitution, key processes in the restoration of the endothelium adjacent to the post-injury lesion site.
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PMID:Influence of GSH synthesis inhibition on temporal distribution of NAD+/NADH during vascular endothelial cells proliferation. 2571 32


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