UMLS:C0020473 - FACTA Search

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

In the present study we compared the vascular reactivity and integrity of the nitric oxide (NO)-cyclic 3',5'-guanosine monophopsphate (cGMP) pathway in carotid arteries of hyper- and normolipidemic rabbits. Vasodilation to acetylcholine, nitroglycerin, and sodium nitroprusside was desensitized in hyperlipidemia, but the nitroprusside-induced relaxation was normalized by an NO synthase inhibitor in endothelium-intact and -denuded vessels. Hyperlipidemic carotid arteries exhibited increased basal NO (detected by EPR spin-trapping) and reactive oxygen species formation (detected by chemiluminescence), whereas acetylcholine-induced NO formation was nearly abolished. Hyperlipidemia increased NADPH-dependent superoxide formation in carotid membranes, and carotid cryosections stained with the fluorescent dye dihydroethidium revealed increased endothelial and medial reactive oxygen species formation. Hyperlipidemia elicited macrophage invasion into the carotid wall, as detected by a dot-immunoblot. The basal activity of cGMP-dependent proteinkinase, the nitroprusside-stimulated activity of soluble guanylyl cyclase, and its protein expression were decreased by hyperlipidemia. The cGMP phosphodiesterase activity was marginally increased by hyperlipidemia, such that the ratio of cGMP-forming vs. -degrading capacity was decreased by 2-fold. Hyperlipidemia triggers infiltration of macrophages into the carotid wall and endothelial as well as smooth muscle superoxide formation. Consequently, relaxation of the carotid arteries are impaired due to smooth muscle and endothelial dysfunction.
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PMID:Mechanisms underlying dysfunction of carotid arteries in genetically hyperlipidemic rabbits. 1659 5

Asymmetric dimethylarginine (ADMA) is synthesized during the methylation of protein arginine residues by protein arginine methyltransferases (PRMT) and is released during proteolysis. ADMA is a competitive inhibitor of nitric oxide synthase and may decrease NO availability. ADMA is eliminated by renal excretion or is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) to citruline and dimethylamine. Two other endogenous methylarginines are also synthesized by PRMT: N-monomethyl-L-arginine (L-NMMA) and symmetric dimethylarginine (SDMA). L-NMMA inhibits NO synthase but its concentrations in circulation are much lower than ADMA whereas SDMA is inactive. Plasma concentration of ADMA is markedly increased in patients with chronic renal failure and moderately increased in patients with many other diseases including hyperlipidemia, diabetes mellitus, arterial hypertension, hyperhomocysteinemia and heart failure. The increased concentration of ADMA is positively correlated with markers of atherosclerosis, such as carotid artery intima-media thickness and has a predictive value for acute cardiovascular events in prospective studies. Angiotensin-converting enzyme inhibitors, angiotensin AT1 receptor antagonists, vitamin E and, according to some studies, estrogens used in hormonal replacement therapy reduce plasma ADMA concentration, which may contribute to their beneficial effect on NO synthesis and endothelial function. However, in some states associated with excess of NO, such as septic shock or excitotoxic neuronal injury ADMA may be protective by limiting toxic effect of high concentrations of NO. This article reviews the effect of pharmacotherapy on ADMA metabolism and its possible clinical implications.
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PMID:Asymmetric dimethylarginine (ADMA) as a target for pharmacotherapy. 1670 18

Previously, we have demonstrated that chronic consumption of a high-fat, high-refined sugar (HFS) diet results in metabolic syndrome which is marked by obesity, insulin resistance, hyperlipidemia, and hypertension in Fischer rats. Metabolic syndrome in this model is associated with oxidative stress, avid nitric oxide (NO) inactivation by reactive oxygen species (ROS), diminished NO bioavailability, and dysregulation of NO synthase isotypes. Although occurrence of oxidative stress and its impact on NO metabolism are well established, the molecular source(s) of ROS in this model is unknown. In an attempt to explore this issue, we measured protein expressions of the key ROS-producing enzyme, NAD(P)H oxidase, and the main antioxidant enzymes, superoxide dismutase (CuZn SOD and Mn SOD), catalase, glutathione peroxidase (GPX), and heme oxygenase-2 (HO-2), in the kidney and aorta of Fischer rats fed an HFS or low-fat, complex-carbohydrate diet for 7 months. In addition, plasma lipid peroxidation product (malondialdehyde) as well as endothelium-dependent and -independent vasorelaxation (aorta rings) was determined. The results showed a significant upregulation of gp91(phox) subunit of NAD(P)H oxidase and downregulations of SOD isoforms, GPX, and HO-2 in the kidney and aorta of the HFS-fed animals. This was associated with increased plasma malondialdehyde concentration and impaired vasodilatory response to acetylcholine, but not the NO donor, Na nitroprusside. The latter findings confirm the presence of oxidative stress and endothelial dysfunction in the HFS-fed rats. Oxidative stress and endothelial dysfunction in the diet-induced metabolic syndrome are accompanied by upregulation of NAD(P)H oxidase, pointing to increased ROS production capacity, and downregulation of SOD isoforms, GPX, and HO-2, the key enzymes in the antioxidant defense system.
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PMID:Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome. 1678 66

Aging is an inevitable biological process associated with increased oxidative stress and accumulation of asymmetric dimethylarginine (ADMA) a known endogenous inhibitor of nitric oxide synthase. Atherosclerosis and IR constitute major risk factors for cardiovascular mortality in elderly with chronic kidney disease (CKD). We investigated the impact of catechin, vitamins E and C supplementation on insulin sensitivity, redox state, ADMA, nitrate and nitrite (NO(2)(-)/NO(3)(-)) levels and histological picture of heart and large blood vessels of aged rats with CRF. Findings of the present study revealed that aging in rats is associated with hyperinsulinemia, hyperlipidemia, IR indicated by higher homeostasis model assessment (HOMA)-index, increased lipid peroxidation product malondialdehyde (MDA), ADMA, and blood pressure (BP), but decreased antioxidant capacity and NO(2)(-)/NO(3)(-) levels. CRF exaggerated all these findings and caused thickened intima of carotid arteries and myocardial hypertrophy. Treatment with catechin, vitamins E and C increases the antioxidant capacity and NO(2)(-)/NO(3)(-) production but, decreases MDA, ADMA and BP levels. Also it keeps insulin sensitivity and normal intima/media thickness of carotid arteries. We conclude that decreased nitric oxide (NO) availability due to ADMA accumulation may be responsible for IR and associated atherosclerotic changes in aged rats with CRF. Catechin, vitamins E and C supplementation may moderate oxidative stress of renal failure, prevent ADMA accumulation, and counteract IR and atherosclerotic changes in the elderly.
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PMID:Catechin combined with vitamins C and E ameliorates insulin resistance (IR) and atherosclerotic changes in aged rats with chronic renal failure (CRF). 1741 8

Previous studies have reported that isohumulones, the bitter compounds in beer, improve insulin resistance and hyperlipidemia in several animal models. In this study, we examined whether isohumulones ameliorate renal injury. Dahl salt-sensitive hypertensive rats were fed a low-salt diet (LS), a high-salt diet (HS) or a high-salt diet containing 0.3% isohumulones (HS+IH) for 4 weeks. Urinary nitrite/nitrate (NOx) excretion was measured at 4 weeks along with blood pressure and urinary protein excretion. Renal injury was evaluated histologically and reactive oxygen species (ROS) and nitric oxide (NO) production in the renal cortex was visualized. Oxidative stress and NO synthase (NOS) expression were evaluated by immunohistochemical staining and Western blot analysis. Mean blood pressure was significantly decreased in the HS+IH group compared with the HS group at 4 weeks (158.1+/-8.7 vs. 177.5+/-3.7 mmHg; p<0.05). Isohumulones prevented the development of proteinuria in the HS+IH group compared with the HS group at 2 weeks (61.7+/-26.8 vs. 117.2+/-9.8 mg/day; p<0.05). Glomerulosclerosis and interstitial fibrosis scores were significantly decreased in the HS+IH group compared with the HS group (0.61+/-0.11 vs. 1.55+/-0.23, 23.7+/-6.8 vs. 36.1+/-3.5%; p<0.05 for both). In the HS group, increased ROS and decreased NO were observed in glomeruli in vivo. Isohumulones reduced the ROS production, leading to the restoration of bioavailable NO. Urinary NOx excretion was significantly increased in the HS+IH group compared with the HS group. Furthermore, renal nitrotyrosine was increased in the HS group compared with the LS group, and this effect was prevented by isohumulones. Renal NOS expression did not differ among the three groups. These results suggest that isohumulones may prevent the progression of renal injury caused by hypertension via an anti-oxidative effect.
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PMID:Isohumulones derived from hops ameliorate renal injury via an anti-oxidative effect in Dahl salt-sensitive rats. 1746 Mar 88

Amla (Emblica officinalis Gaertn.) is widely used in Indian medicine for the treatment of various diseases. We have investigated the effects of amla on the lipid metabolism and protein expression involved in oxidative stress during the ageing process. SunAmla or ethyl acetate extract of amla, a polyphenol-rich fraction, was administered at a dose of 40 or 10 mg/kg body weight per d for 100 d to young rats aged 2 months and aged rats aged 10 months. The lipid levels, such as cholesterol and TAG, in serum and liver were markedly elevated in aged control rats, while they were significantly decreased by the administration of amla. The PPARalpha is known to regulate the transcription of genes involved in lipid and cholesterol metabolism. The PPARalpha protein level in liver was reduced in aged control rats. However, the oral administration of amla significantly increased the hepatic PPARalpha protein level. In addition, oral administration of amla significantly inhibited the serum and hepatic mitochondrial thiobarbituric acid-reactive substance levels in aged rats. Moreover, the elevated expression level of bax was significantly decreased after the oral administration of amla, while the level of bcl-2 led to a significant increase. Furthermore, the expressions of hepatic NF-kappaB, inducible NO synthase (iNOS), and cyclo-oxygenase-2 (COX-2) protein levels were also increased with ageing. However, amla extract reduced the iNOS and COX-2 expression levels by inhibiting NF-kappaB activation in aged rats. These results indicate that amla may prevent age-related hyperlipidaemia through attenuating oxidative stress in the ageing process.
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PMID:Amla (Emblica officinalis Gaertn.) prevents dyslipidaemia and oxidative stress in the ageing process. 1750 15

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

Left ventricular hypertrophy (LVH) is an early manifestation of cardiovascular target organ damage in patients with arterial hypertension. It is not only a target organ response to increased after-load, but is also the most potent cardiovascular risk factor. LVH is multifactorial sign which has several causative factors in addition to blood pressure. Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. ADMA plasma levels have been shown to be elevated in diseases related to endothelial dysfunction such as hypertension, hyperlipidemia, diabetes mellitus. Because cardiac remodeling is associated with endothelial NO pathway, some recent studies investigated whether the plasma ADMA was related to LVH and found that there is a link between ADMA and left ventricular mass and geometry. ADMA was two times higher in patients with concentric LVH than in those normal controls. In many experimental systems, accumulation of ADMA is accompanied by reduced dimethylarginine dimethylaminohydrolase (DDAH) activity. Plasma ADMA is cleared in small part by urinary excretion, but the bulk of ADMA is degraded by DDAH. Therefore, we proposed that change in DDAH activity could disturb the metabolism of ADMA and result in hypertensive LVH through the ADMA/NO pathway.
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PMID:Dimethylarginine dimethylaminohydrolase (DDAH)--a critical regulator of hypertensive left ventricular hypertrophy? 1798 7

Guggulsterone has been used to treat hyperlipidemia, arthritis, and obesity. Although its anti-inflammatory and anti-hyperlipidemic effects have been well documented, the effect of guggulsterone on pancreatic beta cells is unknown. Therefore, in this study, the effect of guggulsterone on IL-1beta- and IFN-gamma-induced beta-cell damage was investigated. Treatment of RINm5F (RIN) rat insulinoma cells with IL-1beta and IFN-gamma induced cell damage, and this damage was well correlated with nitric oxide (NO) and prostaglandin E2 (PGE2) production. However, guggulsterone completely prevented cytokines-mediated cytotoxicity, as well as NO and PGE2 production, and these effects were correlated with reduced levels of the inducible form of NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA and protein expressions. The molecular mechanism by which guggulsterone inhibits iNOS and COX-2 gene expressions appeared to involve the inhibition of NF-kappaB activation. The cytoprotective effects of guggulsterone were also mediated through the suppression of the JAK/STAT pathway. Cells treated with the cytokines downregulated the protein level of SOCS-3, however pretreatment with guggulsterone attenuated this decrease. Additionally, in a second set of experiments in which rat islets were used, the findings regarding the beta-cell protective effects of guggulsterone were essentially the same as those observed when RIN cells were used; guggulsterone prevented cytokines-induced NO and PGE2 production, iNOS and COX-2 expressions, JAK/STAT activation, NF-kappaB activation, downregulation of SOCS-3, and impairment of glucose-stimulated insulin secretion. Collectively, these results suggest that guggulsterone may be used to preserve functional beta-cell mass.
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PMID:Guggulsterone, a plant sterol, inhibits NF-kappaB activation and protects pancreatic beta cells from cytokine toxicity. 1834 24

Cardiovascular (CVS) morbidity and mortality in the end-stage renal disease (ESRD) patients on peritoneal dialysis therapy is 10-30 folds higher than in general population. The prevalence of well known traditional risk factors such as age, sex, race, arterial hypertension, hyperlipidaemia, diabetes, smoking, physical inactivity is higher in the uraemic patients. Besides these, there are specific, nontraditional risk factors for dialysis patients. Mild inflammation present in peritoneal dialysis (PD) patients which can be confirmed by specific inflammatory markers is the cause of CVS morbidity and mortality in these patients. Hypoalbuminaemia, hyperhomocysteinaemia and a higher level of leptin are important predictors of vascular complications as well as CVS events in the PD patients. Plasma norepinephrine, an indicator of sympathetic activity, is high in the ESRD patients and higher in the PD patients than in the patients on haemodialysis (HD). Therefore, norepinephrine may be a stronger risk factor in the PD patients. The same applies to asymmetric dimethylargine (ADMA), an endogenous inhibitor of nitric oxide synthase, which is an important risk factor of CVS morbidity and mortality 15 % higher in the PD than the HD patients. Hyperphosphataemia, secondary hyperparathyroidism and high calcium x phosphate product have been associated with the progression of the coronary artery calcification and valvular calcifications and predict all-cause CVS mortality in the PD patients. Residual renal function (RRF) declines with time on dialysis but is slower in the PD than the HD patients. RRF decline is associated with the rise of proinflammatory cytokines and the onset of hypervolaemia and hypertension which increase the risk of CVS diseases, mortality in general and CVS mortality. In conclusion, it is very important to establish all CVS risk factors in the PD patients to prevent CVS diseases and CVS mortality in this population.
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PMID:[Cardiovascular morbidity and mortality risk factors in peritoneal dialysis patients]. 1879 34

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