Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trends in chronic diseases provide insights into strategies required to improve population health. The authors determined prevalence and multiple-adjusted population attributable risk (PAR) estimates of chronic diseases because of lifestyle factors among Australian adults between 1989-90 and 2004-5, accounting for demographic factors. Between 1989-90 and 2004-5, prevalence increased for diabetes (3.8-6.0%, P < 0.001) and high cholesterol (11.3-13.9%, P < 0.001), but decreased for high blood pressure (21.4-20.4%, P = 0.003) and cardiovascular disease (CVD, 6.2-5.4%, P < 0.001). Prevalence increased for body mass index (BMI) 25-29.9 (30.3-34.9%, P < 0.001), BMI 30-34.9 (7.4-13.5%, P < 0.001) and BMI 35+ (2.1-5.4%, P < 0.001), but decreased for metabolic equivalent-hours per week (MET-hr/week) 0 (36.8-33.1%, P < 0.001) and current smokers (27.6-24.4%, P < 0.001). Diabetes, high cholesterol and high blood pressure burden increased mostly for 60+ years, lowest income quintiles and high BMI (30-34.9 and 35+). Diabetes and CVD burden increased mostly for MET-hr/week 0. Many chronic disease cases would have been theoretically prevented if adults had no prior exposure to BMI 25-29.9 (PAR 9-17%), BMI 30+ (PAR 1-14%) and MET-hr/week 0 (PAR 6-14%). Reducing exposure to lifestyle hazards across the lifespan is required for reversing the rising burden of chronic diseases. Decreases in CVD and high blood pressure prevalence were likely due to targeted improvements in health care, indicating that more can and should be done.
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PMID:Chronic disease trends due to excess body weight in Australia. 1941 99

Erectile dysfunction (ED) is a highly prevalent disease affecting millions of men worldwide with a tendency for widespread increase. ED is now considered an early manifestation of atherosclerosis and, consequently, a precursor of systemic vascular disease. Atherosclerosis and ED share potentially modifiable risk factors, as smoking or high-fat food intake, but it is unclear how regular consumption of anti-oxidant rich drinks, which exhibit recognised anti-atherosclerotic features, affects ED progression. The objective of this study was to evaluate the modulating effects of chronic consumption of catechin-rich beverages on the vascular structure of the rat corpus cavernosum, and how this could contribute to delay or prevention of the onset of ED. Male Wistar rats aged 12 months were treated with green tea (GT) or a green tea extract solution (GTE) as the only liquid source for 6 months. Consumption of GT and GTE led to decreased plasma androgen levels without any significant change in plasma lipid levels. A reduction in corpus cavernosum intracellular storage of lipids, associated with decreased expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR2 in endothelial cells, was observed. Taken together, these results suggest diminished atherosclerotic progression in cavernous tissue. However, functional studies will be necessary to elucidate if catechin-rich beverages are useful compounds in the prevention of deleterious vascular events associated with ED. It was also demonstrated that regular consumption of catechins reduces atherosclerotic progression and mortality due to cardiovascular disease. The results reported here suggest diminished atherosclerotic progression in cavernous tissue in aged rats following chronic ingestion of catechin-rich beverages.
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PMID:Does regular consumption of green tea influence expression of vascular endothelial growth factor and its receptor in aged rat erectile tissue? Possible implications for vasculogenic erectile dysfunction progression. 1942 45

Increased plasma levels of lactosylceramide (LacCer) have been associated with cardiovascular disease. However, it is largely unknown whether LacCer directly contributes to dysfunction of smooth muscle cells (SMCs), a key event in vascular lesion formation. In the present study, we determined the effects and potential mechanisms of LacCer on cell migration and proliferation in human aortic SMCs (AoSMCs). Cell migration and proliferation were determined by a modified Boyden chamber assay and nonradioactive colorimetric (MTS) assay, respectively. We found that LacCer significantly induced AoSMC migration and proliferation in a concentration- and time-dependent manner. In addition, LacCer significantly upregulated the expression of PDGFR-B, integrins (alpha(v) and beta(3)), and matrix metalloproteinases (matrix metalloproteinase-1 and -2) at both mRNA and protein levels, as determined by real-time PCR and Western blot analyses, respectively. Furthermore, LacCer increased superoxide anion production and the transient phosphorylation of ERK1/2 in AoSMCs, as determined by dihydroethidium staining and immunoassay, respectively. Accordingly, LacCer-induced cell migration and proliferation were effectively blocked by antioxidants (seleno-l-methionine and Mn tetrakis porphyrin) and by a specific ERK1/2 inhibitor. Thus, LacCer promotes cell migration and proliferation through oxidative stress and activation of ERK1/2 in AoSMCs. These findings demonstrate the functional role of LacCer in the vascular disease pathogenesis.
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PMID:Lactosylceramide promotes cell migration and proliferation through activation of ERK1/2 in human aortic smooth muscle cells. 1946 42

Preoperative preparation of patients with cardiovascular disease is best initiated by the general practitioner. Updated Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery have been published by the American Heart Association und American College of Cardiology (2007). Individual cardiac evaluation must take into account active cardiac conditions, functional capacity, additional clinical risk factors and surgical risk. Stable, asymptomatic patients with normal functional capacity can proceed to elective anesthesia and surgery without further cardiac evaluation. Active cardiac conditions require evaluation and treatment by a cardiology service prior to elective surgery. In stable patients with poor (<4 metabolic equivalents, MET) or unknown functional capacity and clinical risk factors, who are scheduled for intermediate- or high-risk surgery, further cardiac evaluation and preparation is to be considered. Established indicated beta blocker and statin medication is to be continued; timely institution of beta blocker medication (target heart rate, <65 bpm) may be required depending on the risk of surgery, the presence of coronary heart disease, and the number of clinical risk factors present. Following percutaneous coronary intervention, specific waiting periods are required prior to elective surgery. In patients on antiplatelet therapy, the risk of stopping it should be weighed against the benefit of reduction in bleeding complications from the planned surgery.
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PMID:[Preoperative preparation of patients with cardiovascular disease for noncardiac surgery]. 1956 47

There is great clinical interest in cell-based therapies for ischemic tissue repair in cardiovascular disease. However, the regenerative potential of these therapies is limited due to poor cell viability and minimal retention following application. We report here the development of bioactive peptide amphiphile nanofibers displaying the fibronectin-derived RGDS cell adhesion epitope as a scaffold for therapeutic delivery of bone marrow derived stem and progenitor cells. When grown on flat substrates, a binary peptide amphiphile system consisting of 10 wt.% RGDS-containing molecules and 90wt.% negatively charged diluent molecules was found to promote optimal cell adhesion. This binary system enhanced adhesion 1.4-fold relative to substrates composed of only the non-bioactive diluent. Additionally, no enhancement was found upon scrambling the epitope and adhesion was no longer enhanced upon adding soluble RGDS to the cell media, indicating RGDS-specific adhesion. When encapsulated within self-assembled scaffolds of the binary RGDS nanofibers in vitro, cells were found to be viable and proliferative, increasing in number by 5.5 times after only 5 days, an effect again lost upon adding soluble RGDS. Cells encapsulated within a non-bioactive scaffold and those within a binary scaffold with scrambled epitope showed minimal viability and no proliferation. Cells encapsulated within this RGDS nanofiber gel also increase in endothelial character, evident by a decrease in the expression of CD34 paired with an increase in the expression of endothelial-specific markers VE-Cadherin, VEGFR2 and eNOS after 5 days. In an in vivo study, nanofibers and luciferase-expressing cells were co-injected subcutaneously in a mouse model. The binary RGDS material supported these cells in vivo, evident by a 3.2-fold increase in bioluminescent signal attributable to viable cells; this suggests the material has an anti-apoptotic and/or proliferative effect on the transplanted bone marrow cells. We conclude that the binary RGDS-presenting nanofibers developed here demonstrate enhanced viability, proliferation and adhesion of associated bone marrow derived stem and progenitor cells. This study suggests potential for this material as a scaffold to overcome current limitations of stem cell therapies for ischemic diseases.
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PMID:Development of bioactive peptide amphiphiles for therapeutic cell delivery. 2623 45

Long-lived people may have a unique genetic makeup that makes them more resistant than the general population to prevalent age-related diseases; however, not much is known about genes involved in the longevity. To identify susceptibility variants controlling longevity, we performed a high-throughput candidate gene study using 137 Koreans over 90 yr old and 213 young healthy Koreans. We evaluated 463 informative markers located in 176 candidate genes mostly for diabetes mellitus, cardiovascular disease and cancer under five genetic models. We estimated the odds ratios for each allele, genotype, haplotype, and gene-gene interaction using logistic regression analysis. Associations between 13 genes and longevity were detected at a P-value less than 0.01. Particularly, the rs671 (A) allele of the aldehyde dehydrogenase 2 family (mitochondrial) (ALDH2) gene was associated with longevity only in men (OR 2.11, P =0.008). Four genes, proprotein convertase subtilisin/kexin type 1 (PCSK1, P=0.008), epidermal growth factor receptor (EGFR, P=0.003), paired box 4 (PAX4, P=0.008), and V-yes-1 Yamaguchi sarcoma viral related oncogene homolog (LYN, P=0.002) consistently yielded statistical evidence for association with longevity. The findings of the current study may provide a starting point for future studies to unravel genetic factors controlling longevity in Koreans.
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PMID:Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans. 1964 80

Iron-induced cardiovascular disease is the leading cause of death in iron-overloaded patients. Deferasirox is a novel, once daily oral iron chelator that was recently approved for the treatment of transfusional iron overload. Here, we investigate whether deferasirox is capable of removing cardiac iron and improving iron-induced pathogenesis of the heart using the iron overload gerbil model. Animals were randomly divided into three groups: control, iron overload, and iron overload + deferasirox treatment. Iron-dextran was given 100 mg/kg per 5 days i.p for 10 weeks. Deferasirox treatment was taken post iron loading and was given at 100 mg/kg/day p.o for 1 or 3 months. Cardiac iron concentration was determined by inductively coupled plasma atomic emission spectroscopy. Compared with the untreated group, deferasirox treatment for 1 and 3 months decreased cardiac iron concentration 17.1% (P = 0.159) and 23.5% (P < 0.05), respectively. These treatment-associated reductions in cardiac iron were paralleled by decreases in tissue ferritin expression of 20% and 38% at 1 and 3 months, respectively (P < 0.05). Using oxyblot analysis and hydroethidine fluorescence, we showed that deferasirox significantly reduces cardiac protein oxidation and superoxide abundance by 36 and 47.1%, respectively (P < 0.05). Iron-induced increase in oxidative stress was also associated with increased phosphorylation of ERK-, p38-, and JNK-mitogen-activated protein kinase (MAPK). Interestingly, deferasirox treatment significantly diminished the phosphorylation of all three MAPK subfamilies. These results suggest that deferasirox may confer a cardioprotective effect against iron induced injury.
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PMID:Deferasirox removes cardiac iron and attenuates oxidative stress in the iron-overloaded gerbil. 1965 Jan 17

Due to the frequency of occurrence of cardiovascular disease and its course full of severe complications, patients with this condition make a special population. This group is the addressee of the preventive actions included in secondary prevention. The goal of these actions is a reduction of frequency of the occurrence of consecutive incidents connected with ischemic heart disease, ischemic stroke and peripheral artery disease. The actions put a special emphasis on the counteraction of significant and negative from the social-economic point of view phenomenon, such as disability and premature deaths. The key role within the frames of the integrated preventive procedure in the patients with cardiovascular disease plays the modification of physical activity, mainly realized as a part of a supervised physical training. The training is a basic element of a systematized cardiac rehabilitation. It was Hellerstain, who as a pioneer in using this kind of rehabilitation in the patients after acute coronary incidents, and in the 1950s began propagating a multi-disciplinary attitude to the cardiac rehabilitation programs. Since WHO's formulation of the first definition of cardiac rehabilitation in 1964, as a result of the achievements of modern invasive cardiology, cardiosurgery and pharmacotherapy, the procedures of treatment of the patients with acute coronary syndrome changed radically. Moreover, a time of their hospitalization has shortened significantly. This fact had an influence on created by many scientific associations the successive development of the standardized process of convalescence, which is cardiac rehabilitation. The Board of Polish Society of Cardiology (PTK), appreciating the rank of the issue, appointed a group of experts to work on the standards of the cardiac rehabilitation, which were published in 2004 in the journal "Folia Cardiologica". Based on the modified in 2003 requirements established by The Working Group of Rehabilitation and Effort Physiology of European Society of Cardiology and the authors' own experiences, they standardize the regulations of the cardiac rehabilitation. What is specially underlined in this document is keeping the regulation of cardiac rehabilitation effects optimization with maximum safety for the patients and recommending wide, not depending on age, access to complex rehabilitation programs, which contains multi-factor interventive actions. Promoting all aspects of the improvement of physical activity, the cardiac rehabilitation programs contribute to the large extent to the positive modification of arthrosclerosis risk factors, the improvement of physical performance and reducing the risk of occurrence of next acute cardiovascular incidences. All the above-mentioned aspects lead to a comeback to active participation in the social life, and consequently have a positive influence on the quality of life of the people with cardiovascular disease. The aim of this work is summing up the present knowledge of cardiac rehabilitation as a basic element of secondary prevention.
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PMID:[Complex cardiac rehabilitation in a strategy of secondary prevention of cardiovascular disease]. 1965 Apr 26

Individuals who live to 85 and beyond without developing major age-related diseases may achieve this, in part, by lacking disease susceptibility factors, or by possessing resistance factors that enhance their ability to avoid disease and prolong lifespan. Healthy aging is a complex phenotype likely to be affected by both genetic and environmental factors. We sequenced 24 candidate healthy aging genes in DNA samples from 47 healthy individuals aged eighty-five years or older (the 'oldest-old'), to characterize genetic variation that is present in this exceptional group. These healthy seniors were never diagnosed with cancer, cardiovascular disease, pulmonary disease, diabetes, or Alzheimer disease. We re-sequenced all exons, intron-exon boundaries and selected conserved non-coding sequences of candidate genes involved in aging-related processes, including dietary restriction (PPARG, PPARGC1A, SIRT1, SIRT3, UCP2, UCP3), metabolism (IGF1R, APOB, SCD), autophagy (BECN1, FRAP1), stem cell activation (NOTCH1, DLL1), tumor suppression (TP53, CDKN2A, ING1), DNA methylation (TRDMT1, DNMT3A, DNMT3B) Progeria syndromes (LMNA, ZMPSTE24, KL) and stress response (CRYAB, HSPB2). We detected 935 variants, including 848 single nucleotide polymorphisms (SNPs) and 87 insertion or deletions; 41% (385) were not recorded in dbSNP. This study is the first to present a comprehensive analysis of genetic variation in aging-related candidate genes in healthy oldest-old. These variants and especially our novel polymorphisms are valuable resources to test for genetic association in models of disease susceptibility or resistance. In addition, we propose an innovative tagSNP selection strategy that combines variants identified through gene re-sequencing- and HapMap-derived SNPs.
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PMID:Genetic variation in healthy oldest-old. 1968 May 56

The mammalian Na(+)/H(+) exchanger isoform 1 (NHE1) is a ubiquitously expressed membrane protein that regulates intracellular pH in the myocardium and other tissues. NHE1 is an important mediator of myocardial damage that occurs after ischemia-reperfusion injury. It has also been implicated in apoptotic damage in many tissues and its expression and activity are elevated in disease states in the myocardium. In this study, we examined the effect of additional exogenous NHE1 expression on isolated cardiomyocytes susceptibility to ischemia/reperfusion damage. Exogenous NHE1 elevated Na(+)/H(+) exchanger expression and activity when introduced into isolated cardiomyocytes through an adenoviral system. Isolated cardiomyocytes were subjected to simulated ischemia and reperfusion after infection with either control or NHE1-containing adenovirus. Cells were placed into an anaerobic chamber and effects of NHE1 expression after hypoxia/reoxygenation were examined. Hypoxia/reoxygenation increased caspase-3-like activity in controls, and the effect was greatly magnified in cells expressing NHE1 protein. It also elevated the percentage of apoptotic cardiomyocytes, which was also aggravated by expression of NHE1 protein. Hypoxia/reoxygenation also increased phospho-ERK levels. Elevated NHE1 expression was coincidental with increased expression of the ER stress protein, protein disulfide isomerase (PDI) and calreticulin (CRT). Our results demonstrate that increased NHE1 protein expression makes cells more susceptible to damage induced by hypoxia/reoxygenation in isolated cardiomyocytes. They suggest that elevated NHE1 in cardiovascular disease could predispose the human myocardium to enhanced apoptotic damage.
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PMID:Overexpression of the NHE1 isoform of the Na(+)/H (+) exchanger causes elevated apoptosis in isolated cardiomyocytes after hypoxia/reoxygenation challenge. 1994 39


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