Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complications of pregnancy have been found to be related with thrombophilic polymorphisms that explain about 30% of obstetric complications. We evaluated the angiotensin converting enzyme (ACE) and the angiotensin type 1 receptor (AT1R) gene polymorphisms in the renin-angiotensin system (RAS) as possible risk factors for fetal loss. Fifty-nine women with a history of three or more first-trimester fetal losses and 70 healthy women with a history of normal pregnancies were enrolled in this study. Thrombophilic factors, ACE insertion/deletion (I/D) and AT1R A1166C polymorphisms, prothrombin G20210A and factor V Leiden mutations were analyzed. At univariate and multivariate analysis, a significant association between ACE DD and AT1R CC genotype and fetal loss was observed. The effect of the ACE DD genotype on the risk of fetal loss was higher in AT1R C allele carriers. The prevalence of hyperhomocysteinemia (Hcy) (defined as baseline plasma levels higher than the 95% percentile; cut-off, 10.5 micromol/l per l) was significantly higher in women with fetal loss, and an association between Hcy and fetal loss was detected. All patients showed normal antithrombin, protein C, protein S, and plasminogen activator inhibitor-1 (PAI-1) values. The presence of one risk factor not associated with others was found in 33 out of 59 patients (56%); ACE DD genotype was the most prevalent risk factor. Our results identify new possible predictive markers for fetal loss in RAS polymorphisms and Hcy. Large-scale studies are warranted to attribute clinical relevance to these polymorphisms as risk factors for complicated pregnancies.
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PMID:Angiotensin-converting enzyme DD genotype, angiotensin type 1 receptor CC genotype, and hyperhomocysteinemia increase first-trimester fetal-loss susceptibility. 1108 86

Due to its multifarious biological activity the renin-angiotensin system occupies a special position among risk factors of ischemic heart disease. The discovery of I/D polymorphism of the ACE gene led to a better understanding of genetic control of this enzyme. Hyperhomocysteinemia is an independent risk factor of ischemic heart disease. Elevated plasma levels of homocysteine may be due to improper diet (e.g. shortage of folic acid) and/or genetic influence. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of homocysteine. The present study was performed in 100 patients (14 women and 86 men, mean age 54.2 +/- 9.2 years) with a history of myocardial infarction. The control group included 100 patients (10 women and 90 men, mean age 52.3 +/- 10 years) without such history. PCR was used to detect I/D ACE and C677T MTHFR polymorphisms. Genomic DNA was isolated from peripheral blood nuclear cells and amplified by PCR with two pairs of primers flanking the polymorphic regions. The restriction enzyme Hinf I was used to identify genotypes of the MTHFR polymorphism. No difference between both groups was found concerning the distribution of I/D ACE genotypes (31% II, 51% ID, 18% DD in the study group; 30% II, 57% ID, 13% DD in the control group; Tab. 1) or the distribution of C677T MTHFR genotypes (46% CC, 45% CT, 9% TT in the study group; 39% CC, 50% CT, 11% TT in the control group; Tab. 2). There was a significant effect of I/D genotype on ACE activity (IU/L) in the study (II = 18.2 +/- 17.9; ID = 33.5 +/- 19.9; DD = 68.9 +/- 21.9) and in the control group (II = 24.2 +/- 18.1; ID = 31.5 +/- 20.9; DD = 51.4 +/- 19.5; Tab. 3). No correlation was confirmed between ACE or MTHFR genotypes and age at infarction or left ventricular mass (Tabs. 4, 5, 6). The results indicate that neither the I/D ACE nor the C677T MTHFR polymorphisms are associated with risk of myocardial infarction in the Polish population.
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PMID:[Polymorphism of genes coding for angiotensin I converting enzyme and methylenetetrahydrofolate reductase in patients with ischemic heart disease]. 1171 21

The role of vitamin D in left ventricular hypertrophy and cardiac function. Cardiovascular disease is the leading cause of death among patients with end-stage renal disease (ESRD). Traditional cardiac risk factors, as well as other factors specific to the ESRD population such as hyperphosphatemia, elevated calcium and phosphate product, abnormal lipid metabolism, hyperhomocysteinemia, and chronic inflammation play a role in the excessive risk of cardiovascular death in this population. Left ventricular disorders are proven risk factors for cardiac mortality in hemodialysis patients. These disorders are present in incident ESRD patients at rates far above the general population. There is an accumulating body of evidence that suggests that vitamin D plays a role in cardiovascular disease. Abnormal vitamin metabolism, through deficiency of the active form of 1,25-dihydroxyvitamin D(3), and acquired vitamin D resistance through the uremic state, have been shown to be important in ESRD. Vitamin D deficiency has long been known to affect cardiac contractility, vascular tone, cardiac collagen content, and cardiac tissue maturation. Recent studies using vitamin D receptor deficient mice as a model demonstrate a crucial role of vitamin D in regulation of the renin-angiotensin system. Additionally, there is emerging evidence linking treatment with vitamin D to improved survival on hemodialysis and improvement in cardiac function. The emergence of this data is focusing attention on the previously underappreciated nonmineral homeostatic effects of vitamin D that very likely play an important role in the pathogenesis of cardiac disease in ESRD.
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PMID:The role of vitamin D in left ventricular hypertrophy and cardiac function. 1588 12

Hyperhomocysteinemia has been reported to be associated with both vascular structure alteration and increased cardiovascular risk. This study examined whether hyperhomocysteinemia causes increased systemic arterial stiffness, thereby enhancing blood pressure response to stress in hypertensive patients. In 50 treated hypertensive patients, we studied brachial-ankle pulse wave velocity (PWV), a new measure for arterial stiffness, blood pressure response to stress, and blood pressure recovery after stress. Autonomic nervous activities were examined by spectral analysis of blood pressure and RR interval variabilities. Total plasma homocysteine and neurohumoral parameters were determined from fasting blood. Brachial-ankle PWV correlated with age (r=0.64, p<0.001), plasma homocysteine concentration (r=0.35, p<0.05), and systolic blood pressure (SBP) (r=0.62, p<0.001). Higher plasma homocysteine concentration was independently associated with greater brachial-ankle PWV (beta=0.388, p=0.01). We classified the subjects into high homocysteine (7.3 nmol/ml or over) and low homocysteine (7.2 nmol/ml or below) groups. Baseline SBP, plasma renin activity, aldosterone, and norepinephrine concentrations were similar between the two groups. However, the SBP values during stress and the recovery periods were higher in the high homocysteine group than the low homocysteine group even after adjusting for sex and age. The behavior of sympathetic vasomotor activity did not differ between the two groups. These data suggest that higher plasma homocysteine concentration is associated with increased systemic arterial stiffness, which may enhance blood pressure reactivity to stress in hypertensive patients.
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PMID:Higher plasma homocysteine concentration is associated with more advanced systemic arterial stiffness and greater blood pressure response to stress in hypertensive patients. 1694 Jul 2

Methylenetetrahydrofolate reductase (MTHFR) is associated with homocysteine level. In deficit of MTHFR, cardiovascular risk is increased with hyperhomocysteinemia and hypomethionemia. Mutation of the MTHFR gene is associated with the risk for premature cardiovascular diseases. However, the association between MTHFR mutation and cardiovascular risk is still controversial. The purposes of this study were to determine whether MTHFR genotype is associated with cardiovascular risks in hypertensive adolescents and to investigate the association between MTHFR genotype and carotid intima-media thickness (IMT). Forty-three hypertensive adolescents were included in this study. Serum lipid levels, insulin, vitamin B(12), folate, renin, aldosterone, angiotensin converting enzyme, and homocysteine levels were evaluated. The carotid IMT and diameter were estimated by ultrasound. Brachial-ankle pulse wave velocity was also measured. Polymerase chain reaction was conducted to amplify genomic DNA fragment containing C677T position of the MTHFR gene. The height, weight, body mass index, obesity index, arm circumference, fat mass, and fat distribution were significantly greater in patients with C677T mutation. The C677T mutation group showed significantly greater carotid IMT, higher homocysteine, and lower folic acid levels than the normal genotype group. Interpretation of MTHFR genotype might be useful in predicting the development of premature coronary artery disease in hypertensive adolescents.
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PMID:Methylenetetrahydrofolate reductase TT genotype as a predictor of cardiovascular risk in hypertensive adolescents. 1791 66

We sought to determine whether taurine could specifically protect against coronary artery disease during an atherogenic diet and whether taurine affects the lipid profile, metabolites of methionine, and endothelial atherogenic systems. Rabbits were fed one of the following diets for 4 weeks: (1) control diet; (2) 0.5% cholesterol+1.0% methionine; or (3) 0.5% cholesterol+1.0% methionine+2.5% taurine. Endothelial function was examined, and the left main coronary artery atherosclerosis was quantified by stereology and semiquantitative immunohistochemistry to determine the endothelial expression of proteins related to the NO, renin-angiotensin, endoplasmic reticulum, and oxidative stress systems, as well as apoptosis. Taurine normalized hyperhomocysteinemia (P<0.05) and significantly reduced hypermethioninemia (P<0.05) but not lipidemia. The intima:media ratio was reduced by 28% (P=0.034), and atherosclerosis was reduced by 64% (P=0.012) and endothelial cell apoptosis by 30% (P<0.01). Endothelial cell CCAAT/enhancer binding protein homologous protein was normalized (P<0.05). Taurine failed to improve hyperlipidemia, endothelial function, or endothelial proteins related to the NO, renin-angiotensin, and oxidative stress systems. Taurine reduces left main coronary artery wall pathology associated with decreased plasma total homocysteine, methionine, apoptosis, and normalization of CCAAT/enhancer binding protein homologous protein. These results elucidate the antiapoptotic and antiatherogenic properties of taurine, possibly via normalization of endoplasmic reticulum stress.
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PMID:High dietary taurine reduces apoptosis and atherosclerosis in the left main coronary artery: association with reduced CCAAT/enhancer binding protein homologous protein and total plasma homocysteine but not lipidemia. 1939 54

Chronic kidney disease is a pathology progressively increasing in the world. Patients with renal disease have an about 20 times greater chance of dying for cardiovascular disease than to reach the stage of dialysis and, compared to general population, they have a three times greater risk of developing acute myocardial infarction. Based on these considerations, we analyzed the most important metabolic changes that occur in renal failure, predisposing to ischemic heart disease. Changes in lipids and calcium-phosphorus metabolism, inflammation and oxidative stress, hyperhomocysteinemia, renin-angiotensin-aldosterone axis, anemia, left ventricular hypertrophy and albuminuria have been considered.
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PMID:[From kidney disease to ischemic heart disease]. 2157 94

Vascular fibrosis, characterized by reduced lumen diameter and arterial wall thickening attributable to excessive deposition of extracellular matrix (ECM), links with many clinical diseases and pathological progresses including atherosclerosis. It involves proliferation of vascular smooth muscle cell (VSMC), accumulation of ECM and inhibition of matrix degradation. The risk factors associated with cardiovascular disease, including hypertension, hyperglycemia, dyslipidemia and hyperhomocysteinemia (HHcy), are also suggested as initiation and progression factors of vascular fibrosis. Vascular fibrosis has been found to relate to renin-angiotensin-aldosterone system (RAAS), oxidative stress, inflammatory factors, growth factors and imbalance of endothelium-derived cytokine secretion. Angiotensin II (Ang II) and aldosterone, the circulating effector hormones of RAAS, are recognized as responsible for the pathophysiology of vascular fibrosis. Transforming growth factor-beta (TGF-beta) plays a critical role in ECM accumulation and vascular remodeling via up-regulating the production of several agents including connective tissue growth factor (CTGF) and fibroblast growth factor. An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) results in collagen accumulation and adverse matrix remodeling. Aberrant expression or function of peroxisome proliferator-activated receptor gamma (PPAR gamma) is also associated with, and very likely contributes to, the progression of pathological fibrosis and vascular remodeling. In this review, we discuss the pathogenesis of vascular fibrosis in atherosclerosis with focus on the networking among main responsible mediators. The main pathophysiologic factors leading to vascular fibrosis will also be discussed.
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PMID:Vascular fibrosis in atherosclerosis. 2337 82

Myocardial fibrosis, a major pathophysiologic substrate of heart failure with preserved ejection fraction (HFPEF), is modulated by multiple pathways including the renin-angiotensin system. Direct renin inhibition is a promising anti-fibrotic therapy since it attenuates the pro-fibrotic effects of renin in addition to that of other effectors of the renin-angiotensin cascade. Here we show that the oral renin inhibitor aliskiren has direct effects on collagen metabolism in cardiac fibroblasts and prevented myocardial collagen deposition in a non-hypertrophic mouse model of myocardial fibrosis. Adult mice were fed hyperhomocysteinemia-inducing diet to induce myocardial fibrosis and treated concomitantly with either vehicle or aliskiren for 12 weeks. Blood pressure and plasma angiotensin II levels were normal in control and hyperhomocysteinemic mice and reduced to levels lower than observed in the control group in the groups treated with aliskiren. Homocysteine-induced myocardial matrix gene expression and fibrosis were also prevented by aliskiren. In vitro studies using adult rat cardiac fibroblasts also showed that aliskiren attenuated the pro-fibrotic pattern of matrix gene and protein expression induced by D,L, homocysteine. Both in vivo and in vitro studies demonstrated that the Akt pathway was activated by homocysteine, and that treatment with aliskiren attenuated Akt activation. In conclusion, aliskiren as mono-therapy has potent and direct effects on myocardial matrix turnover and beneficial effects on diastolic function.
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PMID:Effects of direct Renin inhibition on myocardial fibrosis and cardiac fibroblast function. 2434 97