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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin as a vascular hormone, apart from its effect on intermediary metabolism, has been considered to play an important role in cardiovascular regulation and pathophysiology of cardiovascular diseases such as essential hypertension, congestive cardiac failure and atherosclerosis. Insulin induces pressor effects by mechanisms of increased sympathetic activity, renal sodium retention and proliferation of vascular smooth muscle cells. On the other hand, accumulating evidence indicates that insulin decreases vascular resistance and increases organ blood flow especially in skeletal muscle tissue, indicating that insulin is a vasodilator. Several mechanisms underlying insulin-induced vasodilation have been proposed. Insulin enhances calcium efflux from vascular smooth muscle cells by activating the plasma membrane Ca(2+)-ATPase and causes hyperpolarization by stimulating Na+, K(+)-ATPase and sodium/potassium pump. Insulin also stimulates nitric oxide (NO) synthase and increases release of NO from vascular endothelium to cause vasodilation. An increase in cyclic AMP levels is induced by insulin, via activation of insulin receptors, beta-adrenoceptors and calcitonin gene-related peptide receptors. However, main cause of mechanisms mediating the vasodilation remain obscure. Hypertension is associated with insulin resistance and hyperinsulinemia. Insulin resistance may contribute to hypertension by sympathetic overactivity, endothelium dysfunction and decreased vasodilator action of insulin. Therefore, insulin must be considered a vasoactive peptide and more investigations are needed to better understand the full significance of the hemodynamic effect of insulin.
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PMID:[Vascular effects of insulin]. 1087 80

Oxidized low density lipoprotein (oxLDL) has been identified as a potentially important atherogenic factor. Atherosclerosis is characterized by the accumulation of lipid and calcium in the vascular wall. OxLDL plays a significant role in altering calcium homeostasis within different cell types. In our previous study, chronic treatment of vascular smooth muscle cells (VSMC) with oxLDL depressed Ca2+(i) homeostasis and altered two Ca2+ release mechanisms in these cells (IP3 and ryanodine sensitive channels). The purpose of the present study was to further define the effects of chronic treatment with oxLDL on the smooth muscle sarcoplasmic reticulum (SR) Ca2+ pump. One of the primary Ca2+ uptake mechanisms in VSMC is through the SERCA2 ATPase calcium pump in the sarcoplasmic reticulum. VSMC were chronically treated with 0.005-0.1 mg/ml oxLDL for up to 6 days in culture. Cells treated with oxLDL showed a significant increase in the total SERCA2 ATPase content. These changes were observed on both Western blot and immunocytochemical analysis. This increase in SERCA2 ATPase is in striking contrast to a significant decrease in the density of IP3 and ryanodine receptors in VSMC as the result of chronic treatment with oxLDL. This response may suggest a specific adaptive mechanism that the pump undergoes to attempt to maintain Ca2+ homeostasis in VSMC chronically exposed to atherogenic oxLDL.
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PMID:Overexpression of SERCA2 Atpase in vascular smooth muscle cells treated with oxidized low density lipoprotein. 1088 39

Recent evidence suggests that oxidant stress plays a major role in several aspects of vascular biology. Oxygen free radicals are implicated as important factors in signaling mechanisms leading to vascular pathologies such as postischemic reperfusion injury and atherosclerosis. The role of intracellular Ca(2+) in these signaling events is an emerging area of vascular research that is providing insights into the mechanisms mediating these complex physiological processes. This review explores sources of free radicals in the vasculature, as well as effects of free radicals on Ca(2+) signaling in vascular endothelial and smooth muscle cells. In the endothelium, superoxides enhance and peroxides attenuate agonist-stimulated Ca(2+) responses, suggesting differential signaling mechanisms depending on radical species. In smooth muscle cells, both superoxides and peroxides disrupt the sarcoplasmic reticulum Ca(2+)-ATPase, leading to both short- and long-term effects on smooth muscle Ca(2+) handling. Because vascular Ca(2+) signaling is altered by oxidant stress in ischemia-related disease states, understanding these pathways may lead to new strategies for preventing or treating arterial disease.
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PMID:Calcium signaling and oxidant stress in the vasculature. 1092 55

Vascular remodeling is a key feature of many pathologic states, including atherosclerosis, or hypertension. Vascular smooth muscle cells participate in determining the vessel structure by several mechanisms such as cell migration, cell growth, or cell death (necrosis or apoptosis). Here we report that thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ -adenosine triphosphatase (ATPase), is able to induce apoptosis in human vascular smooth muscle cells (HVSMCs). Apoptosis was assessed by three different methods: differential chromatin binding dye staining. cytoplasmic histone-associated DNA fragments detection by enzyme-linked immunosorbent assay (ELISA) and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). When HVSMCs were treated for 1 h with thapsigargin (100 nM-10 microM), there was a concentration-dependent increase in both parameters 24 h after the thapsigargin pulse. When a time-course experiment was performed, both parameters were significantly enhanced from 3 to 6 h after the exposure to thapsigargin. We conclude that thapsigargin promotes apoptosis in HVSMCs, providing a useful tool for the study of programmed cell death in human vascular smooth muscle.
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PMID:Thapsigargin induces apoptosis in cultured human aortic smooth muscle cells. 1106 29

Elderly individuals experience a disproportionate burden from cardiovascular disease. Global changes in aging will have a significant impact on the future of medical practice. However, most physicians have little formal training in geriatric medicine and sometimes fail to distinguish disease states from normal aging. Increasingly, it is recognised that a sedentary lifestyle may be responsible for a large fraction of the so-called 'age-related' changes in the cardiovascular system. Nonetheless, well characterised changes do occur in most individuals with aging. Loss of myocytes with subsequent hypertrophy of the remaining cells is usually observed. Calcification involving the conduction and valvular apparatus is seen in most elderly individuals and may predispose to the common arrhythmias of old age. Age-related loss of arterial compliance contributes to isolated systolic hypertension and left ventricular hypertrophy. Despite these changes, for the majority of healthy older adults, cardiac output is well maintained in the basal state through use of the Frank-Starling principle, in the setting of reduced early diastolic filling. Myocardial relaxation is slowed in part due to age-related changes in the sarcoplasmic reticulum Ca2+ ATPase pump. Elevated blood levels of catecholamines contribute to desensitisation to noradrenergic stimulation and this is associated with an age-related decline in maximum achievable heart rate. Changes in the baroreceptor reflex function and decreased sodium conservation may predispose some individuals to orthostatic and postprandial hypotension. The aetiology of cardiovascular aging is under intense study. The most likely mechanisms involve the result of cumulative damage mediated through a variety of insults. Oxidative stress, non-enzymatic glycation, inflammation and changes in cardiovascular gene expression all seem to influence cardiovascular aging. The benefits of exercise continue to be discovered. Endurance-type training has been shown to have a dramatic impact on parameters of cardiovascular aging. Favourable effects are seen in maximum oxygen consumption, diastolic filling, relaxation and arterial stiffness. Some changes such as the maximum heart rate response do not appear to change with conditioning. Pharmacotherapy may afford the opportunity to influence the aging process. Drugs that can reduce age-associated arterial stiffness, cardiac fibrosis and ventricular hypertrophy should prove useful. Antioxidants continue to be a topic of great interest and require more study. Despite some well described changes with aging, most elderly individuals maintain the opportunity for improved cardiovascular function through conditioning. Early recognition and treatment of diseases that are distinguishable from normal aging, including hypertension and atherosclerosis, together with preventive efforts, should reduce the predicted trends in cardiovascular morbidity and mortality among the aged.
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PMID:Clinical implications of physiological changes in the aging heart. 1134 74

The results of research conducted on the cardiomyocytes plasma membranes structural and functional state under the experimental stress and atherosclerosis are displayed in this article. These experimental pathology is determined to be accompanied by some stereotypic quantitative and qualitative modifications occurred in the lipid matrix of the cardiomyocytes plasma membranes--increase of cholesterol content, decrease of phospholipids, accumulation of lisophospholipids and fatty acid. There are demonstrated results that the experimental stress has an atherogenic effect on the plasma membranes of cells by imputting the cholesterol into the membrane even in the intact animals with normal lipid metabolism. All these modifications are also accompanied by the activation of free-radical oxidation. All these changes are capable to lie in the basis of physical and chemical properties mechanism modification of membranes: modification of lipid matrix, change of viscosity, ion-transport properties of cardiomyocytes membranes, oppression of Na+, K(+)-ATPase activity.
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PMID:[Structural-functional status of the cardiomyocyte cell membrane under experimental pathology]. 1159 28

The interaction between low density lipoproteins (LDL) and platelets might play a central role in the development of atherosclerosis in diabetes. The aim of the present study was to investigate whether the glycation of LDL is associated with modifications of their physico-chemical and functional properties and to study the action of glycated LDL (glycLDL) on platelets. LDL and platelets were isolated from 15 healthy subjects. The content of thiobarbituric acid-reactive substances and the generalized polarization of the fluorescent probe Laurdan were determined in LDL glycated in vitro. Platelets were incubated with native LDL, GlycLDL, and minimally oxidized LDL, and the following parameters were evaluated: platelet aggregation, nitric oxide production, intracellular Ca(2+) concentrations, Na(+)/K(+)-adenosine triphosphatase (Na(+)/K(+)-ATPase), and Ca(2+)-ATPase activities. GlycLDL showed increased thiobarbituric acid-reactive substance levels, a red shift of the Laurdan emission maximum, and a decrease in generalized polarization, indicating a higher polarity and a reduced molecular order compared with native LDL. GlycLDL caused a significant increase in platelet nitric oxide production, intracellular Ca(2+) concentration, and aggregating response to ADP; an inhibition of the platelet membrane Na(+)/K(+)-ATPase activity; and a stimulation of Ca(2+)-ATPase activity. Minimally oxidized LDL did not cause statistically significant changes in the parameters studied. The present work demonstrates that glycation induces compositional and structural changes in LDL and suggests that an altered interaction between glycLDL and platelets might play a role in the vascular complications of diabetes.
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PMID:Glycated low density lipoproteins modify platelet properties: a compositional and functional study. 1199 61

An altered interaction between circulating LDL and endothelial cells might be at the basis of the increased prevalence of atherosclerosis in diabetes mellitus. The aim of the present work was to investigate the effect of a short incubation period with LDL from Type 1 diabetic patients in good metabolic control on endothelial cells derived from human aorta (HAEC). Cultured HAEC were incubated for 3 h with culture medium alone (control HAEC), with native LDL from healthy subjects (control LDL), or with native LDL from Type 1 diabetic patients (Type 1 LDL). After the incubation the following parameters were evaluated: endothelial cell nitric oxide synthase (NOS) activity, nitric oxide (NO) and peroxynitrite production, Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities, intracellular Ca(2+) concentration and fluidity of the superficial part of the plasma membrane studied by 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). Moreover, we studied the cellular activation, evaluated by the fluid phase endocytosis of TMA-DPH, and the microetherogeneity of the membrane surface, evaluated by dynamic fluorescence. HAEC incubated with control LDL showed compared with control HAEC: increased anisotropy and exponential lifetime of TMA-DPH, and enhanced TMA-DPH internalization. HAEC incubated with Type 1 LDL showed compared with both control HAEC and HAEC incubated with control LDL: (i) increased Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities, and intracellular Ca(2+) concentration; (ii) increased NOS activity, NO and peroxynitrite production; (iii) increased anisotropy of TMA-DPH; (iv) enhanced internalization of the probe. The exponential lifetime and the width of distribution of TMA-DPH were significantly increased by Type 1 LDL only in comparison with control HAEC. The results suggest that a short-term interaction with LDL from Type 1 diabetic patients causes alterations of the plasma membrane surface and of cellular functions in endothelial cells in a possibly atherogenic way.
Atherosclerosis 2002 Nov
PMID:Activation of human aortic endothelial cells by LDL from Type 1 diabetic patients: an in vitro study. 1220 72

The effect of high-density lipoprotein (HDL) in protecting against atherosclerosis is usually attributed to its role in 'reverse cholesterol transport'. In this process, HDL particles mediate the efflux and the transport of cholesterol from peripheral cells to the liver for further metabolism and bile excretion. Thus, cell-surface receptors for HDL on hepatocytes are chief partners in the regulation of cholesterol homeostasis. A high-affinity HDL receptor for apolipoprotein A-I (apoA-I) was previously identified on the surface of hepatocytes. Here we show that this receptor is identical to the beta-chain of ATP synthase, a principal protein complex of the mitochondrial inner membrane. Different experimental approaches confirm this ectopic localization of components of the ATP synthase complex and the presence of ATP hydrolase activity at the hepatocyte cell surface. Receptor stimulation by apoA-I triggers the endocytosis of holo-HDL particles (protein plus lipid) by a mechanism that depends strictly on the generation of ADP. We confirm this effect on endocytosis in perfused rat liver ex vivo by using a specific inhibitor of ATP synthase. Thus, membrane-bound ATP synthase has a previously unsuspected role in modulating the concentrations of extracellular ADP and is regulated by a principal plasma apolipoprotein.
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PMID:Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. 1251 57

Gene expression profiling was carried out comparing Con A elicited peritoneal macrophages from C57BL6 and FVBN wild-type and apolipoprotein (apo)E knockout mice. An EST, was expressed at higher levels in C57BL6 compared with FVBN mice. mapped to an atherosclerosis susceptibility locus on chromosome 19 revealed in an intercross between atherosclerosis-susceptible C57BL6 and atherosclerosis-resistant FVBN apoE knockout mice. A combination of database search and Northern analysis confirmed that corresponded to 3'-UTR of a hitherto predicted gene, named HspA12A. Blasting the National Center for Biotechnology Information database revealed a closely related homologue, HspA12B. HspA12A and -B have very close human homologues. TaqMan analysis confirmed the increased HspA12A expression (2.6-fold) in elicited peritoneal macrophages from C57BL6 compared with FVBN mice. TaqMan analysis also revealed increased HspA12A and HspA12B expression (87- and 6-fold, respectively) in lesional versus nonlesional portions of the thoracic aorta from C57BL6 apoE knockout mice on a chow diet. In situ hybridization confirmed that both genes were expressed within lesions but not within nonlesional aortic tissue. Blasting of HspA12A and HspA12B against the National Center for Biotechnology Information database (NR) revealed a hit with the Conserved Domain database for Hsp70 (pfam00012.5, Hsp70). Both genes appear to contain an atypical Hsp70 ATPase domain. The BLAST search also revealed that both genes were more similar to primitive eukaryote and prokaryote than mammalian Hsp70s, making these two genes distant members of the mammalian Hsp70 family. In summary, we describe two genes that code for a subfamily of Hsp70 proteins that may be involved in atherosclerosis susceptibility.
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PMID:Two Hsp70 family members expressed in atherosclerotic lesions. 1255 99


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