Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension was induced in young rats by latex encapsulation of both kidneys. By the fourth week, 85% of the renal-encapsulated (RE) rats became hypertensive. Varying degrees of cardiovascular involvement were evident in the moderately to severely hypertensive rats. The level of systolic blood pressure was directly correlated with the width and the volume of zona glomerulosa of the adrenal cortex. Electron microscopy combined with morphometric-stereologic techniques was employed to quantitate change in the adrenal cortex. The cells of both zona glomerulosa and zona fasciculata of RE rats showed significant increases in the volume of the cell, nucleus, smooth endoplasmic reticulum, and lipid droplets; only in the zona glomerulosa cells was the increase in surface area of the smooth endoplasmic reticulum statistically significant. It is suggested that these structural changes associated with renal-encapsulation hypertension are related at least in part to stress of the hypertensive cardiovascular disease.
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PMID:Quantitative ultrastructural study of the rat adrenal cortex in renal encapsulation-induced hypertension. 124 82

High plasma levels of lipoprotein(a) (Lp(a)) and its unique apolipoprotein, apo(a), are an independent risk factor for cardiovascular disease. Plasma Lp(a) levels vary over a 1000-fold range and are determined by the apo(a) locus, which has at least 34 alleles expressing apo(a) isoforms with molecular weights from < 300,000 to > 800,000. In addition, "null" apo(a) alleles produce no detectable plasma apo(a). We used primary cultures of baboon hepatocytes to investigate the molecular basis for null apo(a) phenotypes. Immunoprecipitation of apo(a) after radiolabeling of hepatocytes revealed that some null alleles gave rise to intracellular protein products that were not secreted. Pulse-chase analysis and endoglycosidase digests demonstrated that these proteins were retained in the endoplasmic reticulum. We also examined the molecular basis for the documented inverse correlation between apo(a) size and plasma Lp(a) concentration. Steady-state labeling and pulse-chase analysis of hepatocytes from animals expressing two isoforms of apo(a) revealed that the endoplasmic reticulum residence time of secreted apo(a) isoforms was determined by their size. This accounted for the inverse relationship between isoform size and level of secretion. We conclude that the efficiency of post-translational processing of apo(a) is a major determinant of plasma Lp(a) concentration.
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PMID:Molecular basis for "null" lipoprotein(a) phenotypes and the influence of apolipoprotein(a) size on plasma lipoprotein(a) level in the baboon. 813 43

Estrogen status is known to affect the incidence of cardiovascular disease. Experiments were designed to prove the influences of in vivo estrogen manipulations on vascular hyperpolarization and relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF), and to explore the possible mechanism contributing to the altered EDHF responses in estrogen-deficient states. Mesenteric arteries with intact endothelium were isolated from sham-operated (control), ovariectomized (OVX), or OVX with 17beta-estradiol replacement (OVX + E ) female rats. In the presence of apamin and charybdotoxin, there was no difference between groups in relaxations to the Ca ionophore A23187 and the endoplasmic reticulum Ca -adenosine triphosphatase inhibitor cyclopiazonic acid (CPA). However, N -nitro-L-arginine produced a marked decrease in A23187- and CPA-induced relaxations in OVX compared with control and OVX + E arteries. In control arteries, A23187 and CPA elicited membrane hyperpolarization in a sustained manner. In contrast, A23187 produced only a small and transient hyperpolarizing effect in OVX arteries. OVX also greatly attenuated the sustained pattern of hyperpolarization to CPA. Such changes in hyperpolarizations were not seen in OVX + E arteries. The EDHF-mediated relaxant and hyperpolarizing responses of control arteries to A23187 and CPA were significantly inhibited by the gap junction inhibitor 18 alpha-glycyrrhetinic acid. Immunohistochemical examination for connexin-43 showed that the expression was abundant along the endothelial layer in control and OVX + E arteries, while being much less in OVX arteries. It was concluded that estrogen deficiency specifically impairs EDHF-mediated vascular actions. This may be partly explained by the reduced expression of connexin-43, a protein molecule that could form myoendothelial gap junction channels.
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PMID:Ovariectomy attenuates hyperpolarization and relaxation mediated by endothelium-derived hyperpolarizing factor in female rat mesenteric artery: a concomitant decrease in connexin-43 expression. 1245 28

Stearoyl-CoA desaturase (SCD) (EC 1.14.99.5) is an endoplasmic reticulum-bound enzyme that catalyzes the delta9-cis desaturation of saturated fatty acyl-CoAs, the preferred substrates being palmitoyl- and stearoyl-CoA, which are converted to palmitoleoyl- and oleoyl-CoA, respectively. These monounsaturated fatty acids are used as substrates for the synthesis of triglycerides, wax esters, cholesteryl esters and membrane phospholipids. The saturated to monounsaturated fatty acid ratio affects membrane phospholipid composition and alteration in this ratio has been implicated in a variety of disease states including cardiovascular disease, obesity, diabetes, neurological disease, skin disorders and cancer. Thus, the expression of SCD is of physiological importance in normal and disease states. Several mammalian SCD genes have been cloned. A single human, three mouse and two rat are the best characterized SCD genes. The physiological role of each SCD isoform and the reason for having three or more SCD gene isoforms in the rodent genome are currently unknown. A clue as to the physiological role of the SCD, at least SCD1 gene and its endogenous products came from recent studies of asebia mouse strains that have a natural mutation in the SCD1 gene and a mouse model with a targeted disruption of the SCD1 gene. In this review we discuss our current understanding of the physiological role of SCD in lipid synthesis and metabolism.
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PMID:Role of stearoyl-coenzyme A desaturase in lipid metabolism. 1253 75

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease and accelerates atherosclerosis in apoE-/- mice. Despite the observations that homocysteine causes endoplasmic reticulum (ER) stress and programmed cell death (PCD) in cultured human vascular endothelial cells, the cellular factors responsible for this effect and their relevance to atherogenesis have not been completely elucidated. We report here that homocysteine induces the expression of T-cell death-associated gene 51 (TDAG51), a member of the pleckstrin homology-related domain family, in cultured human vascular endothelial cells. This effect was observed for other ER stress-inducing agents, including dithiothreitol and tunicamycin. TDAG51 expression was attenuated in homozygous A/A mutant eukaryotic translation initiation factor 2 alpha mouse embryonic fibroblasts treated with homocysteine or tunicamycin, suggesting that ER stress-induced phosphorylation of eukaryotic translation initiation factor 2 alpha is required for TDAG51 transcriptional activation. Transient overexpression of TDAG51 elicited significant changes in cell morphology, decreased cell adhesion, and promoted detachment-mediated PCD. In support of these in vitro findings, TDAG51 expression was increased and correlated with PCD in the atherosclerotic lesions from apoE-/- mice fed hyperhomocysteinemic diets, compared with mice fed a control diet. Collectively, these findings provide evidence that TDAG51 is induced by homocysteine, promotes detachment-mediated PCD, and contributes to the development of atherosclerosis observed in hyperhomocysteinemia.
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PMID:TDAG51 is induced by homocysteine, promotes detachment-mediated programmed cell death, and contributes to the cevelopment of atherosclerosis in hyperhomocysteinemia. 1273 77

Numerous epidemiological studies have demonstrated that hyperhomocysteinemia (HHcy) is a strong and independent risk factor for cardiovascular disease. HHcy can result from a deficiency in the enzymes or vitamin cofactors required for homocysteine metabolism. Several hypotheses have been proposed to explain the cellular mechanisms by which HHcy promotes cardiovascular disease, including oxidative stress, endoplasmic reticulum (ER) stress and the activation of pro-inflammatory factors. Studies using genetic- and diet-induced animal models of HHcy have now demonstrated a direct causal relationship between HHcy, endothelial dysfunction and accelerated atherosclerosis. These recently established animal models of HHcy provide investigators with important in vivo tools to (i) further understand the cellular mechanisms by which HHcy contributes to endothelial dysfunction and atherosclerosis, and (ii) develop therapeutic agents useful in the treatment of cardiovascular disease.
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PMID:Hyperhomocysteinemia and its role in the development of atherosclerosis. 1295 Nov 69

The female sex steroid, estradiol 17beta, mediates its effect through its association with estrogen receptor present in the target cell. So far the major emphasis has been given to the genomic actions of the hormone mediated by the nuclear estrogen receptors. Recent years have seen a shift in the ideas revealing the existence of estradiol binding entities both in the plasma membrane and the endoplasmic reticulum. Though the true identity of this membrane associated receptors is far from being known, a functional role for the same have been implicated both at the genomic as well as the non-genomic level. The major focus of the review is to highlight the existence of membrane associated estrogen receptors and receptor-related proteins and the functional roles played by some of them. The signalling events exerted by this class of membrane associated estrogen receptor could partly explain the physiological significance of estrogen in cardiovascular disease, osteoporosis and breast cancer as well as the molecular mechanism associated with xenoestrogen action.
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PMID:Membrane associated estrogen receptors and related proteins: localization at the plasma membrane and the endoplasmic reticulum. 1461 74

Green tea has been receiving considerable attention as a possible preventive agent against cancer and cardiovascular disease. Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea. Using digital calcium imaging and an assay for [3H]-inositol phosphates, we determined whether EGCG increases intracellular [Ca2+] ([Ca2+]i) in non-excitable human astrocytoma U87 cells. EGCG induced concentration-dependent increases in [Ca2+]i. The EGCG-induced [Ca2+]i increases were reduced to 20.9% of control by removal of extracellular Ca2+. The increases were also inhibited markedly by treatment with the non-specific Ca2+ channel inhibitors cobalt (3 mM) for 3 min and lanthanum (1 mM) for 5 min. The increases were not significantly inhibited by treatment for 10 min with the L-type Ca2+ channel blocker nifedipine (100 nM). Treatment with the inhibitor of endoplasmic reticulum Ca2+-ATPase thapsigargin (1 micro M) also significantly inhibited the EGCG-induced [Ca2+]i increases. Treatment for 15 min with the phospholipase C (PLC) inhibitor neomycin (300 micro M) attenuated the increases significantly, while the tyrosine kinase inhibitor genistein (30 micro M) had no effect. EGCG increased [3H]-inositol phosphates formation via PLC activation. Treatment for 10 min with mefenamic acid (100 micro M) and flufenamic acid (100 micro M), derivatives of diphenylamine-2-carboxylate, blocked the EGCG-induced [Ca2+]i increase in non-treated and thapsigargin-treated cells but indomethacin (100 micro M) did not affect the increases. Collectively, these data suggest that EGCG increases [Ca2+]i in non-excitable U87 cells mainly by eliciting influx of extracellular Ca2+ and partly by mobilizing intracellular Ca2+ stores by PLC activation. The EGCG-induced [Ca2+]i influx is mediated mainly through channels sensitive to diphenylamine-2-carboxylate derivatives.
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PMID:Epigallocatechin-3-gallate increases intracellular [Ca2+] in U87 cells mainly by influx of extracellular Ca2+ and partly by release of intracellular stores. 1464 74

The human endothelial cell plasma membrane harbors two subdomains of similar lipid composition, caveolae and rafts, both crucially involved in various essential cellular processes like transcytosis, signal transduction and cholesterol homeostasis. Caveolin-enriched membranes, isolated by either cationic silica or buoyant density methods, were explored by comparing large series of two-dimensional (2-D) maps and subsequent identification of over 100 protein spots by matrix-assisted laser desorption/ionization (MALDI) peptide mass fingerprinting. Improved representation and identification of membrane proteins and valuable information on various post-translational modifications was achieved by the presented optimized procedures for solubilization, destaining and database searching/computing. Whereas the cationic silica purification yielded predominantly known endoplasmic reticulum residents, the cold-detergent method yielded a large number of known caveolae residents, including caveolin-1. Thus, a large part of this subproteome was established, including known (trans-)membrane, signal transduction and glycosyl phosphatidylinositol (GPI)-anchored proteins. Several predicted proteins from the human genome were isolated for the first time from biological samples, including SGRP58, SLP-2, C8ORF2, and XRP-2. These findings and various optimized procedures can serve as a reference to study the differential composition of endothelial cell caveolae and rafts, known to be involved in pathologies like cancer and cardiovascular disease.
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PMID:Comparative proteomics of human endothelial cell caveolae and rafts using two-dimensional gel electrophoresis and mass spectrometry. 1473 May 80

Deficiencies in vitamins or other factors (B6, B12, folic acid, betaine) and genetic disorders for the metabolism of the non-protein amino acid-homocysteine (Hcy) lead to hyperhomocysteinemia (HHcy). HHcy is an integral component of several disorders including cardiovascular disease, neurodegeneration, diabetes and alcoholic liver disease. HHcy unleashes mediators of inflammation such as NFkappaB, IL-1beta, IL-6, and IL-8, increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide (NO), and induces endoplasmic reticulum (ER) stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation, and inflammation. Animal models have played an important role in determining the biological effects of HHcy. ER stress may also be involved in other liver diseases such as alpha (1)-antitrypsin (alpha(1)-AT) deficiency and hepatitis C and/or B virus infection. Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury, study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans, and examine polymorphism of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease.
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PMID:Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury. 1518 90


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