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)

From the clinical standpoint a cardiomyopathy can be classified as primitive when other causes, i.e. ischemic, infiltrative, systemic diseases, can be ruled out. Initial symptoms usually include a progressive dyspnea and fatigue with tachycardia in a patient previously healthy. Congestive heart failure may be the initial manifestation. Angina is often present, not only because of coronary heart disease. Auscultatory findings usually include a gallop rhythm with a third heart sound, not rarely a four-sound gallop. Blood test to evaluate renal and liver function should be performed. The dosage of troponin I and/or troponin T, plasma renin activity, brain natriuretic peptide or endothelins has recently gained some reputation to indicate prognosis, but there is no reason to believe that these measures are superior to cardiopulmonary stress test.
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PMID:[Dilated cardiomyopathy: role of clinical and laboratory evaluation]. 1202 82

The present study aimed to characterize cardiac hypertrophy induced by activation of the renin-angiotensin system in terms of functional alterations on the level of the contractile proteins, employing transgenic rats harboring the mouse renin gene (TGR(mREN2)27). Ca2+-dependent tension and myosin ATPase activity were measured in skinned fiber preparations obtained from TGR(mREN2)27 and from age-matched Sprague-Dawley rats (SPDR). Western blots for troponin I (TnI) and troponin T (TnT) were performed and the phosphorylation status of TnI were evaluated in myocardial preparations. TnT and myosin heavy chain (MHC) isoforms were analyzed by RT-PCR. The pCa/tension relationship was shifted to the right in TGR(mREN2)27 compared to SPDR as indicated by increased Ca2+-concentrations required for half maximal activation of tension (SPDR 5.80, 95% confidence limits 5.77-5.82 vs. TGR(mREN2)27 5.69, 95% confidence limits 5.67-5.72, pCa units), while maximal developed tension was unaltered. Even more pronounced was the shift in the relationship between pCa and myosin-ATPase (SPDR 6.01, 95% confidence limits 5.99-6.03 vs. TGR(mREN2)27 5.77, 95% confidence limits 5.73-5.79, pCa units). The maximal myosin-ATPase activity was reduced in TGR(mREN2)27 compared to SPDR, respectively (211.0 +/- 28.77 micromol ADP/s vs. 271.6 +/- 43.66 micromol ADP/s, P < 0.05). Tension cost (ATPase activity/tension) was significantly reduced in TGR(mREN2)27. The beta-MHC expression was significantly increased in TGR(mREN2)27. There was no isoform shift for TnT (protein and mRNA), as well as TnI, and no alteration of the phosphorylation of TnI in TGR(mREN2)27 compared to SPRD. The present study demonstrates that cardiac hypertrophy, induced by an activation of the renin-angiotensin system, leads to adapting alterations on the level of the contractile filaments, which reduce tension cost.
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PMID:Altered tension cost in (TG(mREN-2)27) rats overexpressing the mouse renin gene. 1706 60

To evaluate survival after acute myocardial infarction (AMI) in nonagenarians, we conducted a retrospective chart review of 177 consecutive patients > or =90 years of age admitted from 2000 to 2006 with a primary diagnosis of AMI confirmed by peak troponin I > or =1.5 microg/L. Mean follow-up was 3.7 years (range 4 months to 6.7 years). Mean age was 93 years, 34% were men, and 60% were Caucasian. Common co-morbidities included hypertension (67%), dyslipidemia (28%), atrial fibrillation (28%), renal insufficiency (27%), dementia (23%), and previous cerebrovascular events (22%). Mean peak troponin was 20 mug/L (range 1.5 to 183 microg/L). Cardiac catheterization was performed within 48 hours in 42 patients (24%) and after 48 hours in 14 patients (8%); 40 patients (23%) received an intervention. Hospital mortality was 15% (n = 27). Survival at 30 days, 90 days, and 1 year were 78%, 69%, and 47%. Independent predictors of shorter survival time by Cox analysis included body mass index <25 kg/m2 (p <0.001), creatinine > or =2.0 mg/dl (p = 0.001), hemoglobin <11.0 g/dl (p = 0.016), and dementia (p = 0.027). Patients receiving aspirin, clopidogrel, beta blockers, and renin-angiotensin system inhibitors appeared to have a lower mortality. In conclusion, AMI in nonagenarians is associated with high mortality, with over 50% of patients dying within one year of presentation; elevated creatinine and lower hemoglobin are strong predictors of adverse prognosis, and lower body mass index and the presence of dementia add independent prognostic significance.
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PMID:Outcomes of acute myocardial infarction in nonagenarians. 1847 45

Agents that block the renin-angiotensin system (RAS), including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, are of proven benefit in patients after ST-segment elevation myocardial infarction (STEMI). However, no studies have evaluated the benefit of pre-event use of RAS inhibitors before STEMI. A retrospective review was performed of patients admitted to a single hospital with the diagnosis of STEMI and without a history of coronary disease or the equivalent, including diabetes mellitus, peripheral vascular disease, or stroke. Patients were stratified according to the use of RAS inhibitors before STEMI. Compared to patients not taking RAS inhibitors, patients who were taking RAS inhibitors had a lower peak troponin I level (79 vs 120 ng/dl, p = 0.016). Of the patients who had medically treated hypertension, those receiving RAS inhibitors had a significantly lower peak troponin I compared to those receiving non-RAS agents (79 vs 130 ng/dl, p = 0.015), despite equivalent blood pressure across the 2 groups. The beneficial effect of RAS inhibitor pretreatment remained when concomitant aspirin and statin use were controlled for. In conclusion, in patients presenting with a first STEMI, pretreatment with RAS inhibitors conferred a cardioprotective effect. The mechanism of this benefit appears to be independent of an effect on blood pressure control and was not wholly due to the effect of concomitant use of other medicines known to be protective in patients with STEMI.
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PMID:Relation of pre-event use of inhibitors of the renin-angiotensin system with myocardial infarct size in patients presenting with a first ST-segment elevation myocardial infarction. 2072 39

Atherosclerotic renal artery stenosis (ARAS) is a predictor of increased morbidity and mortality. However, whether ARAS itself accelerates the arteriosclerotic process or whether ARAS is solely the consequence of atherosclerosis is unclear. We imaged renal arteries of 1561 hypertensive patients undergoing coronary angiography and followed this cohort for 9 years (range, 2.4-15.1 years; median, 31.2 months, interquartile range, 13.4/52.9 months). All patients received aspirin, renin-angiotensin system blockade, statins, and beta blockade as indicated. One hundred seventy-one patients had ARAS >50% diameter stenosis and 126 patients an arteriosclerotic plaque (ARAP) without significant stenosis. Blood pressures were not different in ARAS, ARAP, and non-ARAS patients. After adjustment for cardiovascular risk factors by propensity scores and matched pair analysis, ARAS patients had a lower ejection fraction and more coronary artery disease (CAD) than non-ARAS patients. The same was true for brain natriuretic peptide values, troponin I, and highly sensitive C-reative protein. Over 9 years, more ARAS patients died of any cause (34% vs 23%; P < .05). The prevalence of CAD in ARAP patients was higher than in non-ARAS patients and lower than in ARAS patients. The mortality of the ARAP patients at 9 years was 37%, not different from the ARAS patients. Atherosclerotic renal artery disease appears to be a marker for the severity of atherosclerosis rather than a causative factor for atherosclerosis progression.
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PMID:Long-term follow-up of patients with atherosclerotic renal artery disease. 2332 2

Metabolic acidosis could occur due to either endogenous acids accumulation or bicarbonate loss from the gastrointestinal tract or commonly from the kidney. This study aimed to investigate the possible underlying mechanism(s) of chronic acidosis-induced cardiac contractile and electrical changes in rats. Twenty four adult Wistar rats, of both sexes, were randomly divided into control group and chronic metabolic acidosis group, which received orally 0.28 M NH(4)Cl in the drinking water for 2 weeks. At the end of experimental period, systolic and diastolic blood pressure values were measured. On the day of sacrifice, rats were anesthetized by i.p. pentobarbitone (40 mg/kg b.w.), transthoracic echocardiography and ECG were performed. Blood samples were obtained from abdominal aorta for complete blood count and determination of pH, bicarbonate, chloride, sodium, potassium, troponin I, CK-MB, IL-6, renin and aldosterone levels. Hearts from both groups were studied for cardiac tissue IL-6 and aldosterone in addition to histopathological examination. Compared to control group, chronic metabolic acidosis group showed anemia, significant systolic and diastolic hypotension accompanied by significant reduction of ejection fraction and fraction of shortening, significant bradycardia, prolonged QTc interval and higher widened T wave as well as significantly elevated plasma levels of renin, aldosterone, troponin I, CK-MB and IL-6, and cardiac tissue aldosterone and IL-6. The left ventricular wall of the acidosis group showed degenerated myocytes with fibrosis and apoptosis. Thus, chronic metabolic acidosis induced negative inotropic and chronotropic effects and cardiomyopathy, possibly by elevated aldosterone and IL-6 levels released from the cardiac tissue.
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PMID:Possible mechanisms of cardiac contractile dysfunction and electrical changes in ammonium chloride induced chronic metabolic acidosis in Wistar rats. 2753 10

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.
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PMID:COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. 3235 35