Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aortic stenosis is the most frequent valvular heart disease. Aortic sclerosis is the first characteristic lesion of the cusps, which is considered today as the process similar to atherosclerosis. Progression of the disease is an active process leading to forming of bone matrix and heavily calcified stiff cusps by inflammatory cells and osteopontin. It is a chronic, progressive disease which can remain asymptomatic for a long time even in the presence of severe aortic stenosis. Proper physical examination remains an essential diagnostic tool in aortic stenosis. Recognition of characteristic systolic murmur draws attention and guides further diagnosis in the right direction. Doppler echocardiography is an ideal tool to confirm diagnosis. It is well known that exercise tests help in stratification risk of asymptomatic aortic stenosis. Serial measurements of brain natriuretic peptide during a follow-up period may help to identify the optimal time for surgery. Heart catheterization is mostly restricted to preoperative evaluation of coronary arteries rather than to evaluation of the valve lesion itself. Currently, there is no ideal medical treatment for slowing down the disease progression. The first results about the effect of ACE inhibitors and statins in aortic sclerosis and stenosis are encouraging, but there is still not enough evidence. Onset symptoms based on current ACC/AHA/ESC recommendations are I class indication for aortic valve replacement. Aortic valve can be replaced with a biological or prosthetic valve. There is a possibility of percutaneous aortic valve implantation and transapical operation for patients that are contraindicated for standard cardiac surgery.
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PMID:[Aortic stenosis: from diagnosis to optimal treatment]. 1872 Jul 55

Accelerated atherosclerosis can lead to an increased prevalence of coronary artery disease, heart failure, brain stroke and peripheral arterial disease. Thus, subjects with chronic renal failure are exposed to increased morbidity and mortality from cardiovascular events. A strong and pervasive link exists between kidney failure and cardiac disease. A variety of individual biomarkers have been evaluated and several have been found to successfully predict the outcome in patients with kidney disease. These include markers of myocardial necrosis, such as cardiac troponin T and I, markers of heart failure, such as B-type of natriuretic peptide and its associated inactive N-terminal fragment, markers of systemic inflammation--C-reactive protein, and an endogenous inhibitor of nitric oxide synthase-asymmetric dimethyl arginin. Increased concentrations of C-reactive protein, B-type of natriuretic peptide, asymmetric dimethyl arginine, and troponin predict a high risk of cardiovascular mortality as well as a mortality due to other causes in patients with chronic renal failure or end stage renal disease (Tab. 1, Ref. 33). Full Text (Free, PDF) www.bmj.sk.
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PMID:Cardiac biomarkers and chronic renal diseases. 1883 40

We tested the hypothesis that plasma brain natriuretic peptide (BNP) levels are elevated in patients with acute cerebrovascular diseases (CVD) independent of heart disease, and reflect CVD severity. After careful evaluations for heart disease, the study included 79 consecutive patients with CVD without any evidence of heart disease admitted within 48 h after onset (71+/-10 years), and 26 control subjects without CVD (CT, 67+/-12 years). Ischemic stroke subtypes were defined by the TOAST classification. Large-artery atherosclerosis (LAA, n=27), small-artery occlusion (SAO, n=27), and intracerebral hemorrhage (ICH, n=25) were included. The plasma BNP levels were measured at admission and 1 month later. Stroke severity and brain infarct volume were evaluated. There were no significant differences in the clinical profiles including echocardiographic parameters among the groups. The plasma BNP level (pg/mL) upon admission was higher in LAA (70.6+/-53.9) than in SAO (38.2+/-28.4) and CT (28.5+/-19.9) (both p<0.05). The level in ICH (47.3+/-28.6) was not significantly different from that in CT. The BNP level in ischemic stroke was positively correlated with the NIH Stroke Scale (NIHSS) (rho=0.42, p<0.05) and infarct volume (r=0.34, p<0.05). Brain infarct volume and NIHSS were independent contributors to the plasma BNP level in ischemic stroke. One month later, the BNP level was significantly decreased and was similar in all CVD groups. The plasma BNP level transiently increased in patients with LAA independently of heart disease, and reflected infarct volume and the severity of acute ischemic stroke.
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PMID:Elevated plasma brain natriuretic peptide levels independent of heart disease in acute ischemic stroke: correlation with stroke severity. 1897 47

Advanced glycation end product receptor (RAGE) interaction plays an important role in atherosclerosis. Although exogenously administered soluble form of RAGE (sRAGE) has been shown to suppress the development and progression of atherosclerosis in animals, the kinetics and role of endogenous sRAGE in humans are not fully understood. In this study, to clarify whether endogenous sRAGE could capture and efficiently eliminate RAGE ligands such as circulating AGEs and high-mobility group box-1 (HMGB-1), we investigated the correlation between sRAGE and RAGE ligands and examined independent determinants of serum levels of sRAGE in hypertensive humans. Two-hundred seventy-one consecutive nondiabetic outpatients with essential hypertension (83 male and 188 female; mean age, 76.5 +/- 9.2 years) underwent a complete history, physical examination, and determination of blood chemistries, including serum levels of sRAGE, AGEs, and HMGB-1. Univariate regression analysis showed that serum levels of sRAGE were associated with body mass index (r = -0.313, P < .0001), waist (r = -0.214, P < .0001), alanine aminotransferase (r = -0.172, P = .005), gamma-glutamyltranspeptidase (r = -0.213, P < .0001), 24-hour creatinine clearance (r = -0.348, P < .0001), B-type natriuretic peptide (r = 0.138, P = .027), tumor necrosis factor-alpha (r = 0.138, P = .002), and alcohol intake (r = -0.155, P = .010). By the use of multiple stepwise regression analyses, 24-hour creatinine clearance (P < .0001), gamma-glutamyltranspeptidase (P < .001), body mass index (P = .007), and tumor necrosis factor-alpha (P = .024) remained significant independently. The present study demonstrated for the first time that there was no significant correlation between serum levels of sRAGE and RAGE ligands such as circulating AGEs and HMGB-1 in hypertensive patients. Anthropometric and inflammatory variables and liver and renal function may be the determinants of endogenous sRAGE levels in nondiabetic hypertensive patients.
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PMID:Independent determinants of soluble form of receptor for advanced glycation end products in elderly hypertensive patients. 1921 61

Renal artery stenosis (RAS) is common among patients with atherosclerosis, and is found in 20-30% of individuals who undergo diagnostic cardiac catheterization. Renal artery duplex ultrasonography is the diagnostic procedure of choice for screening outpatients for RAS. Percutaneous renal artery stent placement is the preferred method of revascularization for hemodynamically significant RAS, and is favored over balloon angioplasty alone. Stent placement carries a class I recommendation for atherosclerotic RAS according to ACC and AHA guidelines. Discordance exists between the very high (>95%) procedural success rate and the moderate (60-70%) clinical response rate after renal stent placement, which is likely to be a result of poor selection of patients, inadequate angiographic assessment of lesion severity, and the presence of renal parencyhmal disease. Physiologic lesion assessment using translesional pressure gradients, and measurements of biomarkers (e.g. brain natriuretic peptide), or both, could enhance the selection of patients and improve clinical response rates. Long-term patency rates for renal stenting are excellent, with 5-year secondary patency rates greater than 90%. This Review will outline the clinical problem of atherosclerotic RAS and its diagnosis, and will critically assess treatment options and strategies to improve patients' outcomes.
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PMID:Diagnosis and management of atherosclerotic renal artery stenosis: improving patient selection and outcomes. 1923 98

Meprin is a member of the astacin family of zinc metalloendopeptidases. It is widely distributed in the body, and hydrolyzes and inactivates several endogenous vasoactive peptides, some of which could alter various functions of cells in the arterial wall. We assessed the influence of chronic meprin inhibition by daily administration of actinonin (5mg/kg body weight per day; i.p.) on the development of atherosclerotic changes in ApoE(-/-) mice. Mice were fed a high-fat (21% fat), cholesterol-rich (1% cholesterol) Western-type diet for 16 weeks starting at 10 weeks of age. At 20 weeks of age, randomly selected ApoE(-/-) mice were treated with Western-type diet chow pellets supplemented with commercially available actinonin (meprin-I group) for 6 weeks; the diet of control ApoE(-/-) mice was supplemented with saline (placebo group). There was no difference in body weight, hemodynamic data and serum lipids between the two groups at the end of the dietary period. Meprin-I treatment was found to elevate levels of natriuretic peptides (NPs) in plasma and the vascular wall by radioimmunoassay. Meprin-I treatment also decreased plaque volume and suppressed lipid deposition in carotid arteries. Meprin-I treatment reduced production of reactive oxygen species (ROS) and apoptosis (which are associated with atherosclerosis) in the vascular wall. In in vitro experiments, meprin-I treatment increased NP function on cell apoptosis, proliferation, and intracellular ROS generation in the THP-1 cell line and primary vascular smooth muscle cells (VSMC). These results suggest that the meprin inhibitor actinonin may have a protective role in atherosclerosis, and that meprin inhibition may be therapeutically useful in atherosclerosis prevention. Suppression of degradation in the arteries of endogenously released NPs (particularly atrial natriuretic peptide and brain natriuretic peptide), or other kinins known to have anti-atherosclerotic actions, may at least partially contribute to the inhibitory effects of meprin-I on atherosclerotic changes.
Atherosclerosis 2009 Nov
PMID:A meprin inhibitor suppresses atherosclerotic plaque formation in ApoE-/- mice. 1946 86

A 3-year multicenter, prospective, randomized, open-label trial (ADVANCED-J) compared the effect of an increased dose of angiotensin-II receptor blocker (ARB) with that of a maintenance dose of ARB plus calcium channel blocker (amlodipine) on blood pressure (BP) control, nephropathy and atherosclerosis in patients with type 2 diabetes and hypertension in whom the usual ARB dose failed to control BP. A cross-sectional analysis using baseline data was conducted. Of 316 patients (recruited between September 2004 and December 2005), 228 patients were evaluated by multiple regression analysis using two models after randomization and exclusions. Model 1 assessed 13 baseline variables (age, sex, estimated diabetes duration, estimated hypertension duration, HbA1c, brain natriuretic peptide (BNP), high-sensitive C-reactive protein (hsCRP), triglycerides (TGs), total cholesterol (TCHO), diabetic retinopathy (DMR), systolic morning home BP (HBP), diastolic morning HBP and brachial-ankle pulse wave velocity (baPWV)) for correlation with the urinary albumin creatinine excretion rate (UACR). In model 2, systolic and diastolic morning HBP was replaced by systolic and diastolic office BP. The systolic morning HBP and systolic office BP or diastolic morning HBP and diastolic office BP correlations were weak, but significant (r=0.43 and 0.48, respectively). BNP, HbA1c, DMR and estimated diabetes duration were significantly correlated with UACR in both models 1 and 2. Although systolic office BP did not show a significant correlation with UACR in model 2, systolic morning HBP showed a significant correlation with UACR in model 1. Morning HBP, but not office BP, may be a significant marker of nephropathy in Japanese patients with type 2 diabetes.
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PMID:Morning home blood pressure may be a significant marker of nephropathy in Japanese patients with type 2 diabetes: ADVANCED-J study 1. 1955 3

Hypercholesterolemia is a common accompaniment of atherosclerosis and may be associated with cardiac hypertrophy. To define the mechanistic basis of cardiac hypertrophy in hypercholesterolemia, we fed low-density lipoprotein receptor knockout (LDLR KO) mice regular diet or high cholesterol (HC) diet for 26 weeks. There was clear evidence of cardiomyocyte hypertrophy and collagen deposition in the hearts of LDLR KO mice fed with HC diet, confirmed by histopathology (hematoxylin and eosin and Picrosirius staining) and upregulation of genes for brain natriuretic peptide, alpha-tubulin, transforming growth factor beta1, and connective tissue growth factor (CTGF). These changes were independent of change in blood pressure. The hypercholesterolemic mice hearts showed an upregulation of LOX-1, an oxidized low-density lipoprotein receptor, and angiotensin II type 1 receptor (AT1R) at messenger RNA level. In addition, there was a marked upregulation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and nuclear factor kappaB (NF-kappaB) messenger RNA, indicating overexpression of markers of oxidant stress. A separate group of LDLR KO mice were fed HC diet along with a potent 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor rosuvastatin or a dihydropyridine calcium channel blocker amlodipine. Administration of rosuvastatin or amlodipine reduced the overexpression of genes for LOX-1 and AT1R and associated NADPH oxidase and NF-kappaB. These phenomena were associated with a marked decrease in cardiomyocyte hypertrophy and collagen deposits in and around the cardiomyocytes. In conclusion, this study provides evidence of cardiac hypertrophy and fibrosis in hypercholesterolemia independent of blood pressure change LOX-1 and AT1R act as possible signals for oxidant stress leading to alterations in cardiac structure during hypercholesterolemia. Most importantly, rosuvastatin and amlodipine ameliorate cardiomyocyte hypertrophy and fibrosis.
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PMID:Cardiac hypertrophy during hypercholesterolemia and its amelioration with rosuvastatin and amlodipine. 1968 48

The growing knowledge about genetic influence on cardiovascular diseases (CVD) combined with the recently generated amounts of genomic data hold promise to the identification of new markers for atherosclerotic CVD. Cardiovascular pharmacogenomics and pharmacogenetics have now the potential for leading to identification of genetic contributors and therefore to the development of predictive genetic tests that could optimize drugs efficacy and minimize toxicity. Clinical studies have shown that genetic variations within cytochromes P450 (CYPs), 3-Hydroxyl-3-Methylglutaryl Coenzyme A Reductase (HMGCR) and apolipoprotein E (APOE) genes influence individual's response to lipid lowering statins. Furthermore, development of antagonists or inhibitors of molecules such as peroxisome proliferator-activated receptors (PPARs), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), angiotensin-converting enzyme (ACE), angiotensin receptors and tumor necrosis factor (TNF)-alpha could be another alternative to prevent atherosclerosis. In addition, novel molecules under the name of biologics including family of peptides such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), urocortin, apelin and antimicrobial peptides (AMPs) could be considered as new targets for the prevention and treatment of CVD. In this article, we will focus mainly on recent genomic advances in the development of new markers and therapeutic agents for CVD. We present an array of molecules that could have pharmacological benefit for the treatment of heart disease. We also discuss in details new strategies including biologics, which are actually the focus of companies for clinical development of therapeutic drugs. All these efforts provide optimism and attractive promise to cure CVD.
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PMID:Genomics and the prospects of existing and emerging therapeutics for cardiovascular diseases. 1975 91

HIV infection is associated with left ventricular (LV) dysfunction and accelerated atherosclerosis. These conditions result in elevation of plasma natriuretic peptide (NP) levels. The present study compares N-terminal-pro-BNP (NT-pro-BNP) levels in HIV-infected and -uninfected women and identifies factors influencing NT-pro-BNP levels in HIV-infected women. A total of 454 HIV-infected and 200 HIV-uninfected participants from the Women's Interagency HIV Study (WIHS) had NT-pro-BNP determination. Elevated NT-pro-BNP level was defined using previously determined age stratified cut-off values of >164 ng/liter (age <60 years) and >225 (age > or = 60 years). HIV-infected women were older (41.6 +/- 8.9 vs. 38.9 +/- 10.5 years, p < 0.01) and were more likely to have anemia, hepatitis C virus (HCV) antibodies, and kidney dysfunction than HIV-uninfected women. HIV-infected women had significantly higher NT-pro-BNP levels (142.4 +/- 524.8 vs. 73.6 +/- 115.1 ng/liter, p = 0.01) and a higher prevalence of elevated NT-pro-BNP (12.1% vs. 7.5%; p = 0.08). In univariate analyses, elevated NT-pro-BNP was significantly associated with age, systolic BP, hypertension, anemia, triglyceride levels, kidney disease, and HCV seropositivity, but not HIV infection. In multivariate analysis, elevated NT-pro-BNP levels were significantly associated with anemia and kidney function, and had a borderline association with the presence of HCV antibodies. Among HIV-infected women, NT-pro-BNP levels were not independently associated with measures of severity of infection or with HAART use. Although HIV-infected women have higher NT-pro-BNP levels than HIV-uninfected women, the differences are due to non-HIV factors such as anemia, kidney disease, and HCV coinfection. These findings suggest that natriuretic peptide levels are a global marker of comorbidity in the setting of HIV infection.
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PMID:Elevated NT-pro-BNP levels are associated with comorbidities among HIV-infected women. 1980 14


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