Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proliferation, atrophy and lipoprotein catabolism are nodal points in an intricate network of pathogenetic factors which influence the complex morphogenesis of atherosclerosis with its ambiguous phenotypes. The compiled findings of our group show that leiomuscular atrophy of the arterial media represents a hitherto widely ignored pathogenetic hinge in atherogenesis which is expected to impede intramural transport of low density lipoproteins (LDL), contributes to the formation of atheromatous plaques due to chemical modification of stagnant LDL, and influences the topographic distribution of plaques. Contrary to the age-dependent atrophy seen in the smooth muscle cells of the tunica media, myointimal cells of the intima, the so-called Langhans cells, are prone to proliferation. In part, cellular growth in atherosclerotic lesions seems to be triggered by biosynthesis of endothelin-1 by lipid-storing macrophages. Similar to self-limited tumour growth, proliferation of atherosclerotic lesions in their cellular phase are controlled by p53, P21 and the gene products of MDM2, Bcl-2 and Bax. Apoptotic cell loss eventually leads to fibrotic end stage lesions.
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PMID:Comparative studies on the antagonism of proliferation and atrophy in atherosclerosis. 1021 40

Although stimulation of the beta-adrenergic receptor increases levels of cAMP and activation of the cAMP response element (CRE) in cardiac myocytes, the role of the signaling mechanism regulated by cAMP in hypertrophy and apoptosis is not well understood. In this study we show that protein expression of inducible cAMP early repressor (ICER), an endogenous inhibitor of CRE-mediated transcription, is induced by stimulation of isoproterenol (ISO), a beta-adrenergic agonist with a peak at approximately 12 hours and persisting for more than 24 hours in neonatal rat cardiac myocytes. ICER is also upregulated by phenylephrine but not by endothelin-1. Continuous infusion of ISO also increased ICER in the rat heart in vivo. Overexpression of ICER significantly attenuated ISO- and phenylephrine-induced cardiac hypertrophy but did not inhibit endothelin-1-induced cardiac hypertrophy. Overexpression of ICER also stimulated cardiac myocyte apoptosis. Antisense inhibition of ICER significantly enhanced beta-adrenergic hypertrophy, whereas it significantly inhibited beta-adrenergic cardiac myocyte apoptosis, suggesting that endogenous ICER works as an important regulator of cardiac hypertrophy and apoptosis. Inhibition of CRE-mediated transcription by dominant-negative CRE binding protein inhibited cardiac hypertrophy, whereas it stimulated cardiac myocyte apoptosis, thereby mimicking the effect of ICER. Both ISO and ICER reduced expression of Bcl-2, an antiapoptotic molecule, whereas antisense ICER prevented ISO-induced downregulation of Bcl-2. These results suggest that ICER is upregulated by cardiac hypertrophic stimuli increasing CRE-mediated transcription in cardiac myocytes and acts as a negative regulator of hypertrophy and a positive mediator of apoptosis, in part through both inhibition of CRE-mediated transcription and downregulation of Bcl-2.
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PMID:Inducible cAMP early repressor (ICER) is a negative-feedback regulator of cardiac hypertrophy and an important mediator of cardiac myocyte apoptosis in response to beta-adrenergic receptor stimulation. 1285 70

This study determined whether exercise training prevents pathological hypertrophy in the left ventricle by modulation of myocardial and apoptosis-associated genes. We used spontaneously hypertensive rats (n=15, non-exercise SHR), exercise-trained SHR (n=15, treadmill exercise for 12 weeks), and sedentary Wistar-Kyoto (WKY) rats (n=15). Exercise-trained SHR expressed adaptive changes such as reduced body weight, heart rate, blood pressures, left ventricle wall thickness, lipid profiles, and homocysteine level. The mRNA expression of angiotensin converting enzyme, endothelin-1, and brain natriuretic peptides in the heart was lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR, whereas mRNA expression of caveolin-3 and eNOS in the heart was higher. Bcl-2 protein was higher in the exercise-trained SHR than in the WKY and the non-exercise SHR. In contrast, Bax protein levels were lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR. Furthermore, the levels of the active forms of caspase-3 (20 kDa) were lower in the exercise-trained SHR and in the WKY than in the non-exercise SHR. These findings suggest that exercise training prevents pathological hypertrophy in the left ventricle by modulation of myocardial genes and that it interferes with a signal transduction pathway of apoptosis secondary to the pathological cardiac hypertrophy.
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PMID:Effects of exercise training on pathological cardiac hypertrophy related gene expression and apoptosis. 1658 33

Many space missions have shown that prolonged space flights may increase the risk of cardiovascular problems. Using a three-dimensional clinostat, we investigated human endothelial EA.hy926 cells up to 10 days under conditions of simulated microgravity (microg) to distinguish transient from long-term effects of microg and 1g. Maximum expression of all selected genes occurred after 10 min of clinorotation. Gene expression (osteopontin, Fas, TGF-beta(1)) declined to slightly upregulated levels or rose again (caspase-3) after the fourth day of clinorotation. Caspase-3, Bax, and Bcl-2 protein content was enhanced for 10 days of microgravity. In addition, long-term accumulation of collagen type I and III and alterations of the cytoskeletal alpha- and beta-tubulins and F-actin were detectable. A significantly reduced release of soluble factors in simulated microgravity was measured for brain-derived neurotrophic factor, tissue factor, vascular endothelial growth factor (VEGF), and interestingly for endothelin-1, which is important in keeping cardiovascular balances. The gene expression of endothelin-1 was suppressed under microg conditions at days 7 and 10. Alterations of the vascular endothelium together with a decreased release of endothelin-1 may entail post-flight health hazards for astronauts.
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PMID:Modeled gravitational unloading induced downregulation of endothelin-1 in human endothelial cells. 1734 Jun 22

It has been established that hyperbaric oxygen (HBO) treatment reduces brain edema, decreases infarct volume, contributes to neurological functional recovery and suppresses apoptosis in suture-induced focal cerebral ischemic animal models. In the present study, we evaluated the therapeutic effect of HBO in an endothelin-1-induced focal cerebral ischemia in rats and explored the associated mechanisms of HBO-induced brain protection. One hundred twenty male Sprague-Dawley rats (280 to 320 g) were randomly assigned to sham, focal cerebral ischemia and focal cerebral ischemia treated with HBO groups. Brain water content, neurological function, morphology and molecular biological markers were assessed. HBO (100% O2, 2.5 atmosphere absolute for 2 h) was initiated at 1 h after focal cerebral ischemia. Rats were killed at 24 h to harvest tissues for Western blot or for histology. In HBO-treated animals, an enhanced ratio of Bcl-2 and Bax and a reduced expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in the hippocampus after focal cerebral ischemia were observed. These results indicate that HBO provides brain protection that is probably associated with the inhibition of HIF-1alpha and the elevation of Bcl-2.
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PMID:Therapeutic effects of hyperbaric oxygen in a rat model of endothelin-1-induced focal cerebral ischemia. 1746 8

The study is to explore the potential mechanisms linking fine particles and cardiovascular toxicity. Spontaneous hypertensive rats (SHR) and age-matched wistar kyoto (WKY) rats were exposed by intratracheal instillation to fine particles with the doses of 0.0, 1.6, 8.0 and 40.0mg/kg b.w., respectively. The exposure was conducted once a day, for three continuous days. Twenty-four hours after the last exposure, the rats were killed and the levels of high sensitive C-reactive proteins (hsCRPs), nitrous oxide (NO), D-dimer and endothelin-1 (ET-1) were measured in blood. Reverse transcriptase polymerase chain reaction (RT-PCR) assay assessed the expression of interleukin-1 beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1), ET-1, Bax and Bcl-2 in left ventricle of rats. Meanwhile, cardiac histological lesions were assessed. The expression transforming growth factor-beta 1 (TGF-beta(1)) in left ventricle was measured by immunohistochemical staining. The results showed that the levels of hsCRP, D-dimer, ET-1 and the expression of IL-1beta, ICAM-1, ET-1, Bax and TGF-beta(1) increased in a dose-dependent manner, but NO and Bcl-2 decreased. Cardiac histology demonstrated exacerbated cardiac lesions in SHR when compared to WKY rats. Meanwhile, at the same dose exposed, the levels of hsCRP, d-dimer, ET-1 and the expression of IL-1beta, ICAM-1, ET-1, Bax and TGF-beta(1) were higher in SHR than those in WKY rats. The results indicated that ambient fine particles which entered into lungs could influence the cardiovascular system. When exposed to fine particles, SHR exhibited more severe cardiovascular injury in comparison to WKY rats. The results indicated that the inflammation, endothelial dysfunction, coagulation disorders and imbalance of apoptosis/anti-apoptosis might be the mechanisms of cardiovascular injury induced by fine particles. Different response between SHR and WKY rats after exposed to fine particles indicated that SHR was more susceptible than WKY rats to acute cardiac impairments from fine particle exposure.
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PMID:Acute effects of fine particles on cardiovascular system: differences between the spontaneously hypertensive rats and wistar kyoto rats. 2002 42

Stellate ganglion block (SGB) is a blockade of sympathetic ganglia innervating the head and neck, and is known to function through vasodilation of the target region. However, the effectiveness of SGB in relieving cerebral vasospasm (CVS) through dilation of intracerebral vessels has not been evaluated. The aim of the present study is to investigate the therapeutic effects of SGB in a rat model of subarachnoid hemorrhage (SAH) complicated by delayed CVS, and explore the underlying mechanisms. The SAH model was established by double injection of autologous arterial blood into the cisterna magna. We simulated SGB by transection of the cervical sympathetic trunk (TCST), and measured changes in the diameter, perimeter and cross-sectional area of the basilar artery (BA) and middle cerebral artery (MCA) to evaluate its vasodilatory effect. To investigate the underlying mechanisms, we determined the expression level of vasoactive molecules endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP) in the plasma, and apoptotic modulators Bcl-2 and Bax in the hippocampus. We found a significant increase in the diameter, perimeter and cross-sectional area of the BA and right MCA in SAH rats subjected to TCST. Application of SGB significantly reduced the expression of ET-1 while increasing that of CGRP in SAH rats. We also found a significant increase in the expression of Bcl-2 and decrease in the expression of Bax in the hippocampus of SAH rats subjected to TCST, when compared to untreated SAH rats. The mechanism of action of SGB is likely mediated through alterations in the ratio of ET-1 and CGRP, and Bax and Bcl-2. These results suggest that SGB can alleviate the severity of delayed CVS by inducing dilation of intracerebral blood vessels, and promoting anti-apoptotic signaling. Our findings provide evidence supporting the use of SGB as an effective and well-tolerated approach to the treatment of CVS in various clinical settings.
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PMID:Protective effect of stellate ganglion block on delayed cerebral vasospasm in an experimental rat model of subarachnoid hemorrhage. 2512

Objectives. Elevated plasma homocysteine (Hcy) could lead to endothelial dysfunction and is viewed as an independent risk factor for atherosclerosis. Heat shock protein 27 (HSP27), a small heat shock protein, is reported to exert protective effect against atherosclerosis. This study aims to investigate the protective effect of HSP27 against Hcy-induced endothelial cell apoptosis in human umbilical vein endothelial cells (HUVECs) and to determine the underlying mechanisms. Methods. Apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) of normal or HSP27-overexpressing HUVECs in the presence of Hcy were analyzed by flow cytometry. The mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Results. We found that Hcy could induce cell apoptosis with corresponding decrease of nitric oxide (NO) level, increase of endothelin-1 (ET-1), intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) levels, elevation of ROS, and dissipation of MMP. In addition, HSP27 could protect the cell against Hcy-induced apoptosis and inhibit the effect of Hcy on HUVECs. Furthermore, HSP27 could increase the ratio of Bcl-2/Bax and inhibit caspase-3 activity. Conclusions. Therefore, we concluded that HSP27 played a protective role against Hcy-induced endothelial apoptosis through modulation of ROS production and the mitochondrial caspase-dependent apoptotic pathway.
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PMID:HSP27 Inhibits Homocysteine-Induced Endothelial Apoptosis by Modulation of ROS Production and Mitochondrial Caspase-Dependent Apoptotic Pathway. 2719 Sep 88

Endothelial dysfunction is a hallmark of a wide range of cardiovascular diseases and is often linked to oxidative stress and inflammation. Our earlier study reported the formation of a functional heterodimer between bradykinin receptor 2 (B2R) and dopamine receptor 2 (D2R) that may modulate cell responses, dependent on intracellular signaling. Here, for the first time, we showed a cooperative effect of these receptors on the modulation of processes involved in oxidative stress, inflammation, and apoptosis in endothelial cells. Sumanirole, a specific D2R agonist, was shown to diminish the excessive production of reactive oxygen species induced by bradykinin, a proinflammatory B2R-activating peptide. This effect was accompanied by modified activities of antioxidant enzymes and increased phosphorylation of endothelial nitric oxide synthase, leading to enhance NO production. In turn, endothelial cell co-stimulation with B2R and D2R agonists inhibited the release of interleukin-6 and endothelin-1 and modulated the expression of apoptosis markers, such as Bcl-2, Bcl-xL, Bax, and caspase 3/7 activity. All these observations argue that the D2R agonist counteracts the pro-oxidative, pro-inflammatory, and pro-apoptotic effects induced through B2R, finally markedly improving endothelial functions.
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PMID:Influence of bradykinin B2 receptor and dopamine D2 receptor on the oxidative stress, inflammatory response, and apoptotic process in human endothelial cells. 3042 93

A number of studies have investigated the effects of ischemic injury on functional and cellular characteristics of hippocampus. There is only a limited study on vascular remodeling of it. The present study aimed at examining vascular remodeling in hippocampus and spatial memory disturbances after transient brain ischemia. Male Wistar rats were randomly divided into four groups, i.e. sham operated (SHAM), transient brain ischemia with 1 day reperfusion (IR1), 3 day reperfusion (IR3), and 10 days reperfusion (IR10) groups. Transient brain ischemia was induced by bilateral common carotid artery occlusion (BCCAO). The spatial memory test was performed using the Morris water maze (MWM) in SHAM and IR10 groups. The rats were euthanized at day 1, 3 or 10 after BCCAO depending on the groups. The mRNA expressions of SOD2, Bcl-2, NeuN, eNOS, endothelin-1 (ET-1), CD31, VE-cadherin and vascular remodeling of the hippocampus were examined. There were deteriorations of spatial learning ability in IR10 group. The percentages of SOD2 and Bcl-2, the expression of NeuN, decreased and the vascular remodeling was observed in the ischemic groups. The eNOS and CD31 expressions were less in IR10, the VE-cadherin expression was less in all ischemic groups than in SHAM group, while ET-1 expression in IR1 group was higher than any other groups. The spatial memory deterioration after BCCAO is associated with vascular remodeling in hippocampus, characterized by lumen narrowing and smooth muscle thickening of microvessels.
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PMID:Spatial Memory Disturbance Following Transient Brain Ischemia is Associated with Vascular Remodeling in Hippocampus. 3066 39


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