Gene/Protein Disease Symptom Drug Enzyme Compound
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 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our review examines the nature of serum amyloid A, its isoforms and, their structure, the manner of induction of the acute phase forms and argument for and against their possible physiological function (s). In this context, the possible role of serum amyloid A as a prognostic indicator of unstable angina and its significance in relation to cardiovascular disease is discussed.
Pediatr Pathol Mol Med
PMID:Acute phase serum amyloid A, cholesterol metabolism, and cardiovascular disease. 1205 4

How we age as individuals is no doubt a complex interaction of genetic and environmental factors. Studies of certain populations with optimal environments and health-related behaviors, as well as twin studies, suggest that the average set of genetic variations should facilitate the average person's ability to live to around age 85. Average life expectancies are lower than this because we generally fight survival advantage with bad health habits that can lead to premature aging, chronic illness, and death at a significantly younger age. Centenarians on the other hand live 15-25 years beyond what the average collection of us are able to achieve. Many of them have a history of aging relatively slowly, and either markedly delaying or even escaping lethal diseases associated with aging (Alzheimer's disease, stroke, cancer, cardiovascular disease, and diabetes). In order to live to such old age, centenarians are less likely to have genetic and environmental exposures that would cause at least lethal diseases at younger ages. Demographic selection is the drop out within a cohort, of genotypes linked to age-related lethal diseases and premature mortality as the cohort achieves older and older age. The result is a very old cohort that lacks these genotypes relative to younger age groups. Recent pedigree and molecular genetic studies indicate that scientists can use this selection to their advantage in discerning genotypes that play important roles in delaying or escaping diseases such as Alzheimer's disease, and in slowing the aging process.
J Mol Neurosci
PMID:The genetics of exceptional human longevity. 1221 88

ATP-binding cassette transporter A1 (ABCA1) was recently recognized as the mutant molecule responsible for Tangier disease with low HDL levels, accumulation of cholesteryl esters in tissues, and increased risk of cardiovascular disease. Extensive studies for the past 2 years have recognized the critical role of ABCA1 in cholesterol and phospholipid trafficking. Since the removal of cholesterol from tissues is a key step in the prevention of atherosclerosis, significant attention has been focused on this molecule. Natural ABCA1 mutations in Tangier disease (TD) patients and WHAM chickens together with induced mutation in ABCA1 knock-out mice unequivocally established the important role of ABCA1 in maintaining circulating HDL levels and promoting cholesterol efflux from the arterial wall. Mice lacking ABCA1 showed similar phenotypes observed in Tangier disease patients with low levels of HDL. Further understanding of the roles of ABCA1 in lipid transport and atherosclerosis became clear from studies with ABCA1 transgenic mice. These mice showed enhanced cholesterol efflux from macrophages and reduced atherosclerotic lesion formation. The promoter of the ABCA1 gene has been mapped to a large extent, with the exception of cAMP response element. The present review summarizes recent developments on the role of ABCA1 in cholesterol efflux and prevention of atherosclerosis. Given the antiatherogenic properties of ABCA1, this molecule can serve as an appropriate target for developing drugs to treat individuals with low levels of HDL.
Mol Cell Biochem 2002 Aug
PMID:ATP binding cassette transporter A1--key roles in cellular lipid transport and atherosclerosis. 1223 82

Resveratrol (RV), a polyphenolic substance found in grape skin, is proposed to account in part for the protective effect of red wine in the cardiovascular system. Angiotensin II (Ang II)-induced hypertrophy of vascular smooth muscle cells (VSMCs) is a pivotal step in the development of cardiovascular disease. The aims of this study were to test the hypothesis that RV may alter Ang II-mediated hypertrophic VSMC growth and to identify the putative underlying signaling pathways. We show that RV indeed potently inhibits Ang II-induced [(3)H]leucine incorporation in a concentration-dependent manner (50 microM RV, 71% inhibition). Western blot analysis reveals that phosphorylation of Akt/protein kinase B (PKB) and to a lesser extent the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) 1/2, both essentially involved in Ang II-mediated hypertrophy, is dose dependently reduced by RV. Consistent with these results, we show that RV attenuates phosphorylation of the p70 ribosomal protein S6 kinase (p70(S6K)), a kinase downstream of the ERK 1/2 as well as the Akt pathway, that is implicated in Ang II-induced protein synthesis. Upstream of Akt/PKB RV seems to mediate its antihypertrophic effect by inhibiting phosphorylation of the phosphatidylinositol 3-kinase (PI(3)K) rather than by activating phosphatases. In summary, we demonstrate for the first time that RV inhibits Ang II-induced VSMC hypertrophy, possibly by interfering mainly with the PI(3)K/Akt and p70(S6K) but also with the ERK 1/2 signaling pathway. Thus, this study delivers important new insight in the molecular pathways that may contribute to the proposed beneficial effects of RV in cardiovascular disease.
Mol Pharmacol 2002 Oct
PMID:Resveratrol suppresses angiotensin II-induced Akt/protein kinase B and p70 S6 kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle cells. 1223 23

The beneficial effect of plant foods on human health is unmistakable. Time and time again, studies have found foods of plant origin to reduce the risk of most major chronic illnesses suffered by the human population. Possible mechanisms for the preventative effects of these foods are discussed. Each of the plant groups reviewed was found to reduce the risk of one or more of the following: cardiovascular disease, cancer (lung, breast, colon, rectal, prostate, epithelial, stomach, esophageal, oral, pharynx, larynx, urinary tract, endometrium, pancreas, thyroid, liver, ovary, gallbladder, bladder, and kidney), diabetes, hypertension, bone degeneration, diverticulitis, constipation, gallstones, age-related blindness. Almost no evidence was found to suggest a negative effect on health due to consumption of these plant foods. Based on this material and a review of conserved animal signaling molecules we surmise that animals require these chemicals to enhance specific mammalian cellular processes, demonstrating phyto-zooidal signaling. Further, this diet dependency coupling between plants and animals probably evolved because of the abundance of a particular plant material in a local environment, which is now broken because of technological advances. In conclusion, the overwhelming majority of evidence shows that people may significantly decrease their risks of the aforementioned diseases by increasing their intake of these foods since they represent a natural method to enhance animal processes and signaling.
Int J Mol Med 2002 Oct
PMID:Communication between animal cells and the plant foods they ingest: phyto-zooidal dependencies and signaling (Review). 1223 87

It is well known that plasma brain natriuretic peptide (BNP) concentration is elevated in cardiovascular diseases such as congestive heart failure. However, although it has been reported to increase in hemodialysis (HD) patients, little is known about plasma BNP in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Plasma BNP concentrations were measured and compared among CAPD patients (n=32), HD patients (n=63) and healthy volunteers (n=14) as well as those patients without cardiovascular disease. In addition, the correlation between plasma BNP concentration and parameters of echocardiography was examined. Plasma BNP concentration was significantly higher in CAPD patients without cardiovascular disease (n=23) than in healthy volunteers (n=14) (62.1+/-60.6 pg/ml versus 9.7+/-9.7 pg/ml, mean +/- SD, P<0.0001). Furthermore, it had a positive correlation with LVMI (CAPD: r=0.37, P=0.0354; HD: r=0.49, P<0.0001) but a negative correlation with LVEF (CAPD: r=-0.39, P=0.0277; HD: r=-0.40, P=0.0010) in both CAPD and HD patients. When all patients were compared, plasma BNP concentration was significantly lower in CAPD patients (n=32) than in HD patients (n=63) (114.8+/-142.7 pg/ml versus 296.8+/-430.4 pg/ml, P<0.0001). When those patients without cardiovascular disease was compared, it was also significantly lower in CAPD patients (n=23) than in HD patients (n=40) (62.1+/-60.6 pg/ml versus 151.8+/-102.2 pg/ml, P<0.0001). In conclusion, plasma BNP concentration was elevated in CAPD patients and correlated with LVMI and LVEF, suggesting that plasma BNP in CAPD patients may be associated with left ventricular hypertrophy (LVH) and left ventricular systolic dysfunction. In addition, plasma BNP concentration was significantly lower in CAPD patients than in HD patients, suggesting that cardiac load in CAPD patients may be lower than that of HD patients.
Int J Mol Med 2002 Oct
PMID:Significance of brain natriuretic peptides in patients on continuous ambulatory peritoneal dialysis. 1223 93

The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure, bicycle exercise test, electrocardiogram and echocardiography were studied [ P(coronary artery disease) <5%]. Whole-body insulin sensitivity and insulin-stimulated myocardial glucose uptake were measured during hyperinsulinaemic euglycaemic glucose clamp with fluorine-18 fluorodeoxyglucose, and myocardial rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole-body insulin sensitivity ( r=0.51, P<0.05 and r=0.56, P<0.01). The strongest independent association by multivariate linear regression analysis was found between myocardial glucose uptake and hyperaemic blood flow ( r=0.63, P<0.005). We conclude that in healthy elderly subjects, insulin-stimulated myocardial glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity.
Eur J Nucl Med Mol Imaging 2002 Dec
PMID:Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects. 1245 94

Although it is well established that depression is a major risk factor for the development of coronary artery disease and that cerebrovascular disease can be a major contributing factor for the development of depression, the information about the interplay between the central nervous system and cardiovascular disease is still limited. We investigated the angiotensin I converting enzyme (ACE) ID and the G-protein beta3-subunit (Gbeta3) C825T polymorphism in 201 patients with unipolar major depression and 161 ethnically and age-matched controls. Both gene variants have earlier been associated with either cardiovascular disease or affective disorders, making them good candidates for a combined analysis. We found a significant increase in the Gbeta3 T allele (OR = 1.61, 95% CI 1.17-2.2, P = 0.0035) and a marginal altered genotype distribution of the ACE ID polymorphism with decrease in the II genotypes (chi(2) = 6.43, df=3, P = 0.04) in the patients' group. Analysing the data for both genes we found that the combined actions of ACE and Gbeta3 genotypes accumulate in carriers of the ACE D allele (ID and DD) and Gbeta3 TT homozygotes with ID/DD-TT carriers showing a more than five-fold increase in risk for major depression (crude OR = 5.83, 95% CI 1.99-17.08, P = 0.0002). As our study was carried out with depressive patients without serious cardiac impairment at the time of the investigation, we are presently unable to predict whether this combined action of the ACE ID/DD-Gbeta3 TT genotype is increasing the risk for both disorders. Nevertheless our study reports for the first time that the same allelic combination of two genes that have been shown to increase the risk for myocardial infarction (Naber et al, 2000) increase the vulnerability for depressive disorder.
Mol Psychiatry 2002
PMID:Combined action of the ACE D- and the G-protein beta3 T-allele in major depression: a possible link to cardiovascular disease? 1247 13

Serum triglyceride (TG) level is a well-known risk factor for cardiovascular disease, a leading cause of morbidity and mortality in Western countries. Although genome-wide scans for TG have been conducted in several populations, few loci have shown strong evidence for linkage. The Hutterites are a founder population, which practices a communal lifestyle that includes a uniformly high-fat, high-cholesterol diet. We measured serum TG in 485 Hutterites >or=14 years old and performed a genome-wide scan to find genetic determinants of the observed variation in TG levels, using mapping methods that take advantage of the extensive inbreeding and linkage disequilibrium (LD) in this single, 1623-member pedigree. We report two highly significant associations with TG levels, alleles at D2S410 on 2q14 (locus P=5.8 x 10(-6), genome-wide P=0.005) and at IFNA on chromosome 9p21 (locus P=4.3 x 10(-5), genome-wide P=0.024). In each case, homozygosity at the locus is associated with low TG levels, suggesting that alleles at nearby loci may protect against high TG levels.
Hum Mol Genet 2003 Jan 15
PMID:Major loci influencing serum triglyceride levels on 2q14 and 9p21 localized by homozygosity-by-descent mapping in a large Hutterite pedigree. 1249 94

Anthocyanins are the chemical components that give the intense color to many fruits and vegetables, such as blueberries, red cabbages and purple sweet potatoes. Epidemiological investigations have indicated that the moderate consumption of anthocyanin products such as red wine or bilberry extract is associated with a lower risk of cardiovascular disease and improvement of visual functions. Recently, there is increasing interesting in the pharmaceutical function of anthocyanins. This review summarizes current knowledge on the various molecular evidences of cancer chemoprevention by anthocyanins. These mechanisms can be subdivided into the following aspects: 1) the antioxidation; 2) the molecular mechanisms involved in anticarcinogenesis; 3) the molecular mechanisms involved in the apoptosis induction of tumor cells. Finally, the bioavailability and structure-activity relationship of anthocyanins are also summarized.
Curr Mol Med 2003 Mar
PMID:Potential mechanisms of cancer chemoprevention by anthocyanins. 1263 May 61


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