Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite significant progress in renal replacement therapy, the mortality from cardiovascular disease (CVD) in patients with chronic renal failure (CRF) is many times higher than in the general population. The traditional risk factors are frequently present in CRF patients. However, based upon conventional risk factor analysis, these factors do not fully explain the extraordinary increase in morbidity and mortality in CVD among patients with CRF. Accumulating evidence suggests that CRF is associated with impaired endothelial cell function. In recent years, the role of endothelial dysfunction (ED) and excessive oxidative stress (OS) in the development of CVD has been highlighted. ED is an early feature of vascular disease in different diseases such diabetes, hypertension, hypercholesterolemia, and coronary heart disease. The precise mechanism which induces ED is not clear. Several factors however, including OS-related accumulation of uremic toxins, hypertension and shear stress, dyslipidemia with cytotoxic lipoprotein species such as small, dense low-density lipoprotein (LDL) particles, competitive inhibition of endothelial nitric oxide (NO) by increased production by asymmetrical dimethylarginine (ADMA) are pathogenic. In addition, it is known that excessive OS causes ED. An overproduction of reactive oxygen species (ROS) may injure the endothelial cell membrane, inactivate NO, and cause oxidation of an essential cofactor of nitric oxide synthase (NOS). Recent studies have demonstrated that an impaired endothelium-dependent vasodilation and OS are closely related to each other in patients with CRF.
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PMID:Endothelium-dependent vasodilation and oxidative stress in chronic renal failure: impact on cardiovascular disease. 1269 8

In the recent HEMO study, the most common cause of death in dialyzed patients was ischemic heart disease. In Europe there are regional differences, but the mortality due to cardiovascular disease is also very high. The long-lasting controversy whether the high incidence and prevalence of atherosclerotic manifestations (particularly ischemic heart disease) may be explained by known risk factors, or non-traditional risk factors are also involved seems to be partially solved with the increasing evidence that the latter hypothesis is true. Thus, together with classic risk factors such as hypertension, dyslipidemia and diabetes, other situations such as microinflammation, increased concentration of asymmetrical dimethyl-L-arginine, disturbed phosphate metabolism and anemia may represent important risk factors for accelerated atherosclerosis in dialyzed patients.
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PMID:Atherosclerosis in dialyzed patients. 1473 9

Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) increase the risk of adult onset insulin resistance and dyslipidemia in humans and rats. IUGR rats are further characterized by postnatal alterations in hepatic PPAR-gamma coactivator (PGC-1) and carnitine-palmitoyl-transferase I (CPTI) expression, as well as overall hyperacetylation of histone H3. However, it is unknown whether the histone H3 hyperacetylation is site specific or relates to the changes in gene expression previously described in IUGR rats. We therefore hypothesized that uteroplacental insufficiency causes site-specific modifications in hepatic H3 acetylation and affects the association of acetylated histone H3 with PGC-1 and CPTI promoter sequences. Uteroplacental insufficiency was used to produce asymmetrical IUGR rats. IUGR significantly increased acetylation of H3 lysine-9 (H3/K9), lysine-14 (H3/K14), and lysine-18 (H3/K18) at day 0 of life, and these changes occurred in association with decreased nuclear protein levels of histone deacetylase 1 (HDAC1) and HDAC activity. Chromatin immunoprecipitation using acetyl-H3/K9 antibody and day 0 chromatin revealed that uteroplacental insufficiency affected the association between acetylated H3/K9 and the promoters of PGC-1 and CPTI, respectively, in IUGR liver. At day 21 of life, the neonatal pattern of H3 hyperacetylation persisted only in the IUGR males. We conclude that uteroplacental insufficiency increases H3 acetylation in a site-specific manner in IUGR liver and that these changes persist in male IUGR animals. The altered association of the PGC-1 and CPTI promoters with acetylated H3/K9 correlates with previous reports of IUGR altering the expression of these genes. We speculate that in utero alterations of chromatin structure contribute to fetal programming.
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PMID:Uteroplacental insufficiency induces site-specific changes in histone H3 covalent modifications and affects DNA-histone H3 positioning in day 0 IUGR rat liver. 1549 74

Both hypertension and type 2 diabetes mellitus are common and there are no reliable markers either to predict their development or complications. High fat diet and carbohydrate-rich diet enhance serum asymmetrical dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric oxide synthesis. ADMA levels are elevated in patients with hypertension, poor control of hyperglycemia, diabetic microangiopathy and macroangiopathy and dyslipidemia. One of the earliest signs of vascular dysfunction and insulin resistance, which are present in hypertension and type 2 diabetes mellitus, is an elevation in serum ADMA levels. Displacing plasma ADMA by oral supplementation of L-arginine restores endothelial dysfunction by augmenting endothelial nitric oxide generation. Strict control of hyperglycemia decreases serum ADMA levels. These and other studies suggest that serum ADMA levels could be used to predict the development of hypertension and type 2 diabetes mellitus in those who are at high-risk to develop these diseases.
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PMID:L-arginine, NO and asymmetrical dimethylarginine in hypertension and type 2 diabetes. 2119 55

The objective of the study was to determine the effects of a high fat (HF) diet alone or with high fructose (HF/F) on functional and structural changes in the basilar arteries and cardiovascular health parameters in rats. Male Sprague Dawley rats were fed either a HF (30%) or HF/F (30/40%) diet for 12 weeks. The basilar artery was cannulated in a pressurized system (90 cm H2O) and vascular responses to KCl (30 - 120 mM), endothelin (10(-11) - 10(-7) M), acetylcholine (ACh) (10(-10) - 10(-4) M), diethylamine (DEA)-NONO-ate (10(-10) - 10(-4) M), and papaverine (10(-10) - 10(-4) M) were evaluated. Rats were also monitored for food intake, body weight, blood lipids, blood pressure, and heart rate. At death, asymmetrical dimethyl arginine level (ADMA) and leptin were assayed in serum. Although there was no significant difference in weight gain and food intake, HF and HF/F diets increased body fat composition and decreased the lean mass. HF/F diet accelerated the development of dyslipidemia. Although resting blood pressure remained unchanged, stress caused a significant elevation in blood pressure and a modest increase in heart rate in HF fed rats. Both HF and HF/F diet resulted in decreased response to endothelium-dependent and -independent relaxation, whereas increased basilar artery wall thickness was observed only in HF group. Serum leptin levels positively correlated with wall thickness. Moreover serum ADMA was increased and eNOS immunofluorescence was significantly decreased with both diets. These data suggest that the presence of high fructose in a HF diet does not exacerbate the detrimental consequences of a HF diet on basilar artery function.
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PMID:High dietary fructose does not exacerbate the detrimental consequences of high fat diet on basilar artery function. 2722 80

As the most widely consumed endocrine-disrupting chemical, bisphenol A (BPA) has been linked to reproductive dysfunction, diabetes mellitus, and obesity. However, the evidence for an association between BPA and cardiovascular disease (CVD) remains insufficient. In the present study, we aimed to identify the association between BPA and CVD, using data from the 2003-2016 National Health and Nutrition Examination Surveys (NHANES). We estimated urine BPA concentration after adjustments for creatinine (ng/mg) and normalized the asymmetrical distribution using natural logarithmic transformation (ln-BPA/Cr). A multivariate logistic regression was performed to evaluate the odds ratio (OR) and 95% confidence interval (CI) for CVD, with ln-BPA/Cr concentration as predictor. We then performed a Mantel-Haenszel meta-analysis with five eligible studies and NHANES 2003-2016 data. Our subjects were 11,857 adults from the NHANES data. After adjusting for age, sex, race/ethnicity, body mass index (BMI), cigarette smoking, diabetes status, hypertension, and dyslipidemia, OR between ln-BPA/Cr and CVD was 1.13 (95% CI: 1.02-1.24). After propensity-score-matching with age, sex, race/ethnicity, BMI, cigarette smoking, diabetes, hypertension, and dyslipidemia, OR continued to be significant for the association between ln-BPA/Cr and CVD (OR: 1.18, 95% CI: 1.04-1.33). A restricted cubic spline plot of this relationship revealed a dose-dependent increase in OR. However, untransformed BPA had a linear relationship with CVD only at low concentrations, whereas the OR of BPA plateaued at high concentrations. In a meta-analysis with 22,878 subjects, after adjusting for age, sex, and various cardiometabolic risk factors, OR was 1.13 (95% CI, 1.03-1.23). In conclusion, our study provides additional epidemiological evidence supporting an association between BPA and CVD.
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PMID:Effects of bisphenol A on cardiovascular disease: An epidemiological study using National Health and Nutrition Examination Survey 2003-2016 and meta-analysis. 3315 23