Abstract：
:The terminal complement complex C5b-9 is known to participate in inflammatory processes including atherosclerosis. Inflammation appears to be a direct consequence of C5b-9-mediated cell stimulation. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors may exert anti-inflammatory effects on vascular cells independent of lowering plasma cholesterol. Thus, we studied activation of vascular smooth muscle cells (VSMCs) by C5b-9 focusing on whether inhibition of the HMG-CoA reductase can reduce the proinflammatory effects of C5b-9.C5b-9 in sublytic concentrations increased the proliferation of human VSMCs and induced a time-dependent activation of the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase (ERK). Proliferation and ERK1/2 activation could be inhibited by the specific ERK inhibitor PD98059. HMG-CoA inhibition with cerivastatin-reduced VSMC proliferation and C5b-9-induced ERK1/2 activation. Cerivastatin also reduced the C5b-9-induced synthesis of the proinflammatory interleukin-6 (IL-6). Furthermore, C5b-9 induced activation of the transcription factors activator protein- 1 (AP-1) and nuclear factor-kappaB (NF-kappaB), which could be inhibited by pretreatment of VSMCs with cerivastatin. L-mevalonate and geranylgeranylpyrophosphate reversed the inhibitory effects of cerivastatin. The present study in VSMCs shows that cerivastatin inhibits IL-6 synthesis and cell proliferation induced by the terminal complement complex C5b-9. This may be an important mechanism contributing to the beneficial effects of HMG-CoA reductase inhibitors beyond lowering of plasma cholesterol.
journal_name
Basic Res Cardioljournal_title
Basic research in cardiologyauthors
Viedt C,Shen W,Fei J,Kamimura M,Hänsch GM,Katus HA,Kreuzer Jdoi
10.1007/s00395-003-0437-4keywords:
subject
Has Abstractpub_date
2003-11-01 00:00:00pages
353-61issue
6eissn
0300-8428issn
1435-1803journal_volume
98pub_type
杂志文章abstract：:MicroRNAs (miRNAs) are important regulators of adaptive and maladaptive responses in cardiovascular diseases and hence are considered to be potential therapeutical targets. However, their role as novel biomarkers for the diagnosis of cardiovascular diseases still needs to be systematically evaluated. We assessed here ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-010-0123-2
更新日期：2011-01-01 00:00:00
abstract：:We tested the hypotheses that myocardial infarction in mice would lead to progressively worsening heart failure 12-18 weeks later and that exercise testing would provide a suitable means to evaluate left ventricular function sequentially. C57BL/6 mice (n = 69) underwent left coronary artery ligation (n = 50) or thorac...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s003950200013
更新日期：2002-05-01 00:00:00
abstract：:The concept of metabolic coronary flow control provides a rationale for the close relationship of coronary flow and myocardial metabolic rate of oxygen. The concept is based on the presence of an oxygen (metabolic) sensor coupled functionally to effector mechanisms, which control vascular tone. Four modes of metabolic...
journal_title：Basic research in cardiology
pub_type： 杂志文章,评审
doi：10.1007/s00395-006-0621-4
更新日期：2006-11-01 00:00:00
abstract：:Heat shock protein 70 (Hsp70) has been shown to have an anti-apoptotic function, but its mechanism is not clear in heart. In this study, we examined the effect of Hsp70 deletion on AIF-induced apoptosis during ischemia/reperfusion (I/R) in vivo. Although Hsp70 KO and WT mice demonstrated similar amounts of AIF release...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-011-0164-1
更新日期：2011-05-01 00:00:00
abstract：:Pressure-overloaded cardiac hypertrophy was induced by abdominal aortic constriction in 10-week-old male Wistar rats. 24-26 weeks after aortic constriction, the hearts were excised and a myocardial mechanical study was performed using isolated left ventricular papillary muscles. There was no significant difference in ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01907024
更新日期：1987-07-01 00:00:00
abstract：:Conflicting data on the inotropic effect of insulin are present in the literature suggesting a positive inotropic property or no inotropic effect or even a negative influence. To clarify the reason for these diverging findings, dose-response curves of insulin have been performed in isolated working rat and guinea pig ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-002-0350-2
更新日期：2002-07-01 00:00:00
abstract：:The effect of i.v. ergonovine tartrate infusions (0.05-20 micrograms/kg/min, 12 minutes duration) on coronary arteries was studied in 14 conscious dogs instrumented to continuously measure vascular diameter by an ultrasonic dimension gauge using 10-MHz piezoelectric crystals. Ergonovine induced a biphasic coronary res...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01908043
更新日期：1982-05-01 00:00:00
abstract：:In this paper, we review the hypothesis that activated tissue renin-angiotensin systems play a detrimental role in heart failure. The main arguments for this idea are discussed: a) tissue renin-angiotensin systems behave functionally distinct from the circulating renin-angiotensin system; b) tissue renin-angiotensin s...
journal_title：Basic research in cardiology
pub_type： 杂志文章,评审
doi：10.1007/BF00795368
更新日期：1996-01-01 00:00:00
abstract：:In recent years research has shown that muscle is capable of reacting to mechanical stimuli by altering biochemical processes. Myocardium is probably the source of a biochemical factor, or factors which activate myocardial protein synthesis. In experimentally induced cardiac hypertrophy adaptive alterations have been ...
journal_title：Basic research in cardiology
pub_type： 杂志文章,评审
doi：10.1007/BF02070160
更新日期：1983-07-01 00:00:00
abstract：:An increased occurrence of hypertension has been reported among leg-amputees. In order to investigate whether leg amputation is followed by an elevation of sympathetic tone, possibly enhanced by continuous mechanical irritation of the amputation stump by wearing a prosthesis, blood pressure (BP), pulse-rate (PR) and p...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01907771
更新日期：1981-05-01 00:00:00
abstract：:Myocardial stunning, a transient contractile dysfunction that appears following a brief period of ischemia, is at least partly due to the production of oxygen-derived free radicals. The objective of the present study was to determine whether the Ginkgo biloba extract EGb761, which has antioxidant properties in vitro, ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-003-0380-4
更新日期：2003-02-01 00:00:00
abstract：:Pentostatin (2-deoxycoformycin) is a potent inhibitor of adenosine deaminase and has been demonstrated to augment endogenous adenosine levels during regional and global myocardial ischemia. Based on the rationale that increasing endogenous adenosine during ischemia may be cardioprotective, the objective of this study ...
journal_title：Basic research in cardiology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00789447
更新日期：1995-03-01 00:00:00
abstract：:The aim of this study was to examine the effect of ischemic preconditioning on the releases of cardiac troponin T (TnT) during reperfusion in isolated rat hearts. Experiments were done on 22 rat hearts, which were perfused according to the method of Langendorff and were divided into the control group (n = 14) and the ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF00795616
更新日期：1994-05-01 00:00:00
abstract：OBJECTIVE:Chemokines control the migration of leukocytes to inflamed tissue, and in particular monocyte chemoattractant protein (MCP)-1 has been implicated in the pathogenesis of several cardiovascular disorders such as chronic heart failure (CHF) and myocarditis. We hypothesised that MCP-1 may directly contribute to a...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s003950170042
更新日期：2001-07-01 00:00:00
abstract：:Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into contr...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-019-0750-1
更新日期：2019-09-09 00:00:00
abstract：:The purpose of this study was to determine the effect of acute and chronic propranolol on heart size and regional O2 supply/consumption variables in thyroxine (T4)-treated rabbit hearts. New Zealand white rabbits were given 0.5 mg/kg T4 for 3 or 16 days with and without concomitant 2 mg/kg propranolol. Another group w...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01907360
更新日期：1988-05-01 00:00:00
abstract：:In the spontaneously hypertensive rat (SHR) with established hypertension left ventricular mass closely correlated with the proportion of ventricular myosin (VM)-3. A 60% VM-3 content was reached corresponding, under the present housing conditions, to an average age of 40 weeks without any significant change in total ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/978-3-662-11374-5_15
更新日期：1986-01-01 00:00:00
abstract：:Total cholesterol, phospholipids, and triglycerides in serum were studied during myocardial infarction in a patient group treated with glucose, insulin and potassium (GIK), and a conventionally treated group. There was no difference in the typical changes of cholesterol and phospholipids between the groups, but the GI...
journal_title：Basic research in cardiology
pub_type： 临床试验,杂志文章
doi：10.1007/BF01907206
更新日期：1983-11-01 00:00:00
abstract：BACKGROUND:Reopening of the infarct-related coronary artery is the treatment of choice in the clinical setting of acute myocardial infarction. Nevertheless the removal of the total occlusion obtained either by thrombolysis or by primary angioplasty is followed by the ischemia/reperfusion sequelae. One of many proposed ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s003950200049
更新日期：2002-09-01 00:00:00
abstract：:Cardiac glycosides like ouabain are used in the therapy of heart failure and atrial fibrillation. They exert a positive inotropic effect on cardiomyocytes by inhibiting the plasma membrane sodium pump (Na,K-ATPase), decreasing the Ca-extrusion by the sarcolemmal cardiac sodium/calcium exchanger (NCX) and increasing th...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-003-0396-9
更新日期：2003-03-01 00:00:00
abstract：:The PKC hypothesis and its variants are attractive but unproved. The chief difficulty is the lack of an objective means to assess whether or not PKC has been activated in hearts preconditioned in vivo with ischemia or in hearts preconditioned by pharmacologic means. The strongest evidence is supporting the PKC hypothe...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF00797206
更新日期：1997-01-01 00:00:00
abstract：:We investigated the force-frequency relationship (0.5-3 Hz) in non-failing human myocardium and in end-stage failing human myocardium due to dilated cardiomyopathy or subacute myocarditis. In non-failing myocardium, force of contraction increased with increasing stimulation frequency. In end-stage heart failure, the f...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/978-3-642-72474-9_17
更新日期：1992-01-01 00:00:00
abstract：:Phospholamban is a regulatory phosphoprotein which modulates the active transport of Ca2+ by the cardiac sarcoplasmic reticular Ca(2+)-ATPase enzyme (SERCA2) into the lumen of the sarcoplasmic reticulum. Phospholamban, which is a reversible inhibitor of SERCA2, represses the enzyme's activity, and this inhibition is r...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF00794064
更新日期：1997-01-01 00:00:00
abstract：:Short repeated cycles of peripheral ischemia/reperfusion (I/R) can protect distant organs from subsequent prolonged I/R injury; a phenomenon known as remote ischemic preconditioning (RIPC). A RIPC-mediated release of humoral factors might play a key role in this protection and vascular endothelial cells are potential ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-015-0474-9
更新日期：2015-03-01 00:00:00
abstract：:If everything happens strictly according to the natural laws, which meet extremum principles, in what way can the possibility for life be characterised, so that the optimization processes of evolution can take place? Is it legitimate to "enlarge" the natural laws by certain laws of conservation? The question then aris...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：
更新日期：1993-01-01 00:00:00
abstract：:Complete length-tension diagrams of myocardium were measured on isolated papillary muscles of cat right ventricle. These diagrams clearly demonstrate that irrespective of loading conditions there is no uniform maxima curve. As a function of preload the curves of afterloaded isotonic maxima obey totally separate nonlin...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01907862
更新日期：1985-11-01 00:00:00
abstract：:Rat hearts were exposed and injured locally by direct cryoapplication. The hearts were examined 2, 4, 20 and 48 hours, 7 and 12 days later. In the first 48 hours mast cell and polymorphonuclear (mainly eosinophilic) granulocyte infiltration was followed by proliferation of mononuclear phagocytic and fibroblastic cells...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01907742
更新日期：1979-05-01 00:00:00
abstract：:A study of substrate selection in the isolated heart was made using 13C NMR isotopomer analysis, a method that unequivocally identifies relative substrate utilization. This technique has several advantages over conventional approaches used to study this problem. It detects the labeling of metabolic end-products presen...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF00788500
更新日期：1995-09-01 00:00:00
abstract：:Toxic peroxides result when oxygen radicals react with various peroxidic precursors in tissue or blood. A colorimetric method based on reactions of malondialdehyde (MDA), a key intermediate in the formation of peroxides, has been described in fresh tissues. The present report adapts this assay to measure MDA levels in...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01910480
更新日期：1984-09-01 00:00:00
abstract：:Isolated cells obtained from adult myocardium are proving invaluable for a wide range of studies concerned with the mechanisms underlying many important cardiological processes. Although care must always be taken to ensure that the single myocyte is an appropriate model for the particular question to be researched, it...
journal_title：Basic research in cardiology
pub_type： 杂志文章,评审
doi：
更新日期：1985-01-01 00:00:00
