Multitargeted effects of statin-enhanced thrombolytic therapy for stroke with recombinant human tissue-type plasminogen activator in the rat.


BACKGROUND:Microvascular dysfunction posttreatment of stroke with recombinant human tissue-type plasminogen activator (rht-PA) constrains the therapeutic window to 3 hours. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) promote vascular thrombolysis and reduce the inflammation response. We therefore investigated the neuroprotective effects of a combination of atorvastatin and delayed rht-PA treatment in a rat model of embolic stroke. METHODS AND RESULTS:Rats subjected to embolic middle cerebral artery occlusion were treated with atorvastatin in combination with rht-PA 4 hours after stroke. Magnetic resonance imaging measurements revealed that combination treatment with atorvastatin and rht-PA blocked the expansion of the ischemic lesion, which improved neurological function compared with saline-treated rats. Real-time reverse transcription-polymerase chain reaction analysis of single endothelial cells isolated by laser-capture microdissection from brain tissue and immunostaining showed that combination treatment downregulated expression of tissue factor, von Willebrand factor, protease-activated receptor-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9, which concomitantly reduced cerebral microvascular thrombosis and enhanced microvascular integrity. Combination treatment did not increase cerebrovascular endothelial nitric oxide synthase (eNOS) levels or eNOS activity, and inhibition of NOS activity with N-nitro-L-arginine methyl ester did not block the beneficial effects of combination treatment on stroke. Furthermore, combination treatment compared with thrombolytic monotherapy increased cerebral blood flow and reduced infarct volume in eNOS-null mice. CONCLUSIONS:These data demonstrate that combination treatment with atorvastatin and rht-PA exerts a neuroprotective effect when administered 4 hours after stroke and that the therapeutic benefits are likely attributed to its multitargeted effects on cerebrovascular patency and integrity.






Zhang L,Zhang ZG,Ding GL,Jiang Q,Liu X,Meng H,Hozeska A,Zhang C,Li L,Morris D,Zhang RL,Lu M,Chopp M




Has Abstract


2005-11-29 00:00:00














  • Temporal Trends in Percutaneous Coronary Intervention Appropriateness: Insights From the Clinical Outcomes Assessment Program.

    abstract:BACKGROUND:It is unknown whether the appropriate use of percutaneous coronary intervention (PCI) has improved over time and whether trends in PCI appropriateness have been accompanied by changes in the use of PCI. METHODS AND RESULTS:We applied appropriate use criteria to determine the appropriateness of all 51 872 PC...


    pub_type: 杂志文章


    authors: Bradley SM,Bohn CM,Malenka DJ,Graham MM,Bryson CL,McCabe JM,Curtis JP,Lambert-Kerzner A,Maynard C

    更新日期:2015-07-07 00:00:00

  • Transplantation of nanoparticle transfected skeletal myoblasts overexpressing vascular endothelial growth factor-165 for cardiac repair.

    abstract:BACKGROUND:We investigated the feasibility and efficacy of polyethylenimine (PEI) based human vascular endothelial growth factor-165 (hVEGF165) gene transfer into human skeletal myoblasts (HSM) for cell based delivery to the infarcted myocardium. METHODS AND RESULTS:Based on optimized transfection procedure using enha...


    pub_type: 杂志文章


    authors: Ye L,Haider HKh,Tan R,Toh W,Law PK,Tan W,Su L,Zhang W,Ge R,Zhang Y,Lim Y,Sim EK

    更新日期:2007-09-11 00:00:00

  • Exploration of the precision of classifying sudden cardiac death. Implications for the interpretation of clinical trials.

    abstract:BACKGROUND:As cardiovascular clinical trials improve in sophistication and therapies target specific cardiac mechanisms of death, a more objective and precise system to identify specific cause of death is needed. Ideally, sudden cardiac death would describe patients dying of ventricular tachycardia and ventricular fibr...


    pub_type: 杂志文章


    authors: Pratt CM,Greenway PS,Schoenfeld MH,Hibben ML,Reiffel JA

    更新日期:1996-02-01 00:00:00

  • Time-series analysis of heart rate variability during submaximal exercise. Evidence for reduced cardiac vagal tone in animals susceptible to ventricular fibrillation.

    abstract::Periodic fluctuations in the R-R interval have been used as noninvasive measures of cardiac autonomic tone. For example, a reduced heart rate variability has been shown to correlate with an increased mortality in patients recovering from myocardial infarction. The effects that physiologic perturbations such as exercis...


    pub_type: 杂志文章


    authors: Billman GE,Hoskins RS

    更新日期:1989-07-01 00:00:00

  • Sudden death recorded during Holter monitoring.

    abstract::Six instances of sudden death were recorded by Holter monitoring, which showed ventricular fibrillation in five and a bradyarrhythmia in one. Complex ventricular ectopic activity preceded cardiac arrest in five patients, including the one with the bradyarrhythmic arrest. Two patients with chronic bifascicular block ar...


    pub_type: 杂志文章


    authors: Nikolic G,Bishop RL,Singh JB

    更新日期:1982-07-01 00:00:00

  • Use of fresh decellularized allografts for pulmonary valve replacement may reduce the reoperation rate in children and young adults: early report.

    abstract:BACKGROUND:Degeneration of xenografts or homografts is a major cause for reoperation in young patients after pulmonary valve replacement. We present the early results of fresh decellularized pulmonary homografts (DPH) implantation compared with glutaraldehyde-fixed bovine jugular vein (BJV) and cryopreserved homografts...


    pub_type: 杂志文章,多中心研究


    authors: Cebotari S,Tudorache I,Ciubotaru A,Boethig D,Sarikouch S,Goerler A,Lichtenberg A,Cheptanaru E,Barnaciuc S,Cazacu A,Maliga O,Repin O,Maniuc L,Breymann T,Haverich A

    更新日期:2011-09-13 00:00:00

  • Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis.

    abstract:BACKGROUND:Early stages of coronary atherosclerosis are characterized by a mainly functional impairment of coronary vasodilator capacity under the impact of such risk factors as hypercholesterolemia. The goal of this study was to determine whether 6-month cholesterol-lowering therapy improves coronary flow reserve in p...


    pub_type: 临床试验,杂志文章


    authors: Baller D,Notohamiprodjo G,Gleichmann U,Holzinger J,Weise R,Lehmann J

    更新日期:1999-06-08 00:00:00

  • Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association.

    abstract:BACKGROUND:Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute corona...


    pub_type: 杂志文章,meta分析,评审


    authors: Lichtman JH,Froelicher ES,Blumenthal JA,Carney RM,Doering LV,Frasure-Smith N,Freedland KE,Jaffe AS,Leifheit-Limson EC,Sheps DS,Vaccarino V,Wulsin L,American Heart Association Statistics Committee of the Council on Epidemiology an

    更新日期:2014-03-25 00:00:00

  • Nitric oxide modulates myocardial oxygen consumption in the failing heart.

    abstract:BACKGROUND:Endogenous nitric oxide (NO) has been reported to inhibit oxygen consumption in the normal heart, so that nonselective inhibition of NO synthase (NOS) caused an increase of myocardial oxygen consumption (MVO2). Although endothelial NOS responses are depressed in congestive heart failure (CHF), inducible NOS ...


    pub_type: 杂志文章


    authors: Chen Y,Traverse JH,Du R,Hou M,Bache RJ

    更新日期:2002-07-09 00:00:00

  • Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease: vasodilator capacity and cellular mechanisms.

    abstract:BACKGROUND:Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because thes...


    pub_type: 临床试验,杂志文章


    authors: Rimensberger PC,Spahr-Schopfer I,Berner M,Jaeggi E,Kalangos A,Friedli B,Beghetti M

    更新日期:2001-01-30 00:00:00

  • Brain natriuretic peptide enhances renal actions of furosemide and suppresses furosemide-induced aldosterone activation in experimental heart failure.

    abstract:BACKGROUND:The renal actions of brain natriuretic peptide (BNP) in congestive heart failure (CHF) are associated with increased diuresis and natriuresis, preserved glomerular filtration rate (GFR), and lack of activation of the renin-angiotensin-aldosterone system (RAAS). In contrast, diuretic-induced natriuresis may b...


    pub_type: 杂志文章


    authors: Cataliotti A,Boerrigter G,Costello-Boerrigter LC,Schirger JA,Tsuruda T,Heublein DM,Chen HH,Malatino LS,Burnett JC Jr

    更新日期:2004-04-06 00:00:00

  • The new 99mTc myocardial perfusion imaging agents: 99mTc-sestamibi and 99mTc-teboroxime.

    abstract::The two new 99m (99mTc) labeled myocardial perfusion agents, 99mTc-Sestamibi and 99mTc-Teboroxime, are now available for routine clinical application. Both agents allow assessment of ejection fraction by the first-pass technique at rest or during exercise, thus providing additional information not available with thall...


    pub_type: 临床试验,杂志文章,多中心研究,评审


    authors: Berman DS,Kiat H,Maddahi J

    更新日期:1991-09-01 00:00:00

  • Differential effects of green tea-derived catechin on developing versus established atherosclerosis in apolipoprotein E-null mice.

    abstract:BACKGROUND:Oxidative stress has been implicated in vascular injury and atherogenesis, and antioxidant treatment has shown favorable results in preclinical studies. Despite this, antioxidant therapy has failed to show benefit in clinical trials. Failure of antioxidants in clinical trials may be partly because such thera...


    pub_type: 杂志文章


    authors: Chyu KY,Babbidge SM,Zhao X,Dandillaya R,Rietveld AG,Yano J,Dimayuga P,Cercek B,Shah PK

    更新日期:2004-05-25 00:00:00

  • Endothelium-dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease.

    abstract:BACKGROUND:A family history of premature coronary artery disease (CAD) in a first-degree relative is an independent risk factor for coronary disease. Both genetic and environmental influences are likely to be responsible and may interact, but their relative importance is unclear. METHODS AND RESULTS:We studied endothe...


    pub_type: 杂志文章


    authors: Clarkson P,Celermajer DS,Powe AJ,Donald AE,Henry RM,Deanfield JE

    更新日期:1997-11-18 00:00:00

  • Influence of angiotensin-converting enzyme and angiotensin II type 1 receptor gene polymorphisms on aortic stiffness in normotensive and hypertensive patients.

    abstract:BACKGROUND:Clinical and experimental studies have demonstrated a major role of the renin-angiotensin system in the functional and structural changes of the large arteries in hypertension. Because genetic studies may help us to understand the mechanisms underlying the involvement of this system in arterial regulation, t...


    pub_type: 杂志文章


    authors: Benetos A,Gautier S,Ricard S,Topouchian J,Asmar R,Poirier O,Larosa E,Guize L,Safar M,Soubrier F,Cambien F

    更新日期:1996-08-15 00:00:00

  • Cyclosporine impairs release of endothelium-derived relaxing factors in epicardial and resistance coronary arteries.

    abstract:BACKGROUND:Cyclosporin A is reported to impair endothelium-mediated vasorelaxation and induce endothelin release in some noncoronary vascular beds. We wished to determine whether acute cyclosporine administration induces endothelial dysfunction in coronary conductance or resistance arteries. METHODS AND RESULTS:We exa...


    pub_type: 杂志文章


    authors: Sudhir K,MacGregor JS,DeMarco T,De Groot CJ,Taylor RN,Chou TM,Yock PG,Chatterjee K

    更新日期:1994-12-01 00:00:00

  • Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy.

    abstract:BACKGROUND:Atrial fibrillation (AF), the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), is capable of producing symptoms that impact quality of life and is associated with risk for embolic stroke. However, the influence of AF on clinical course and outcome in HCM remains incompletely resolved. ...


    pub_type: 杂志文章


    authors: Rowin EJ,Hausvater A,Link MS,Abt P,Gionfriddo W,Wang W,Rastegar H,Estes NAM,Maron MS,Maron BJ

    更新日期:2017-12-19 00:00:00

  • Identification of 92-kD gelatinase in human coronary atherosclerotic lesions. Association of active enzyme synthesis with unstable angina.

    abstract:BACKGROUND:Acute coronary ischemia is usually initiated by rupture of atherosclerotic plaque, leading to intracoronary thrombosis and clinical sequelae. The proximate cause of plaque rupture is unknown. Accordingly, we investigated the potential role of the 92-kD gelatinase member of the matrix metalloproteinase family...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Brown DL,Hibbs MS,Kearney M,Loushin C,Isner JM

    更新日期:1995-04-15 00:00:00

  • Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women.

    abstract:BACKGROUND:Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance. In the present study, we tested the hypothesis that myocardial fatty acid metabolism...


    pub_type: 杂志文章


    authors: Peterson LR,Herrero P,Schechtman KB,Racette SB,Waggoner AD,Kisrieva-Ware Z,Dence C,Klein S,Marsala J,Meyer T,Gropler RJ

    更新日期:2004-05-11 00:00:00

  • Prospective study of a self-report type A scale and risk of coronary heart disease: test of the MMPI-2 type A scale.

    abstract:BACKGROUND:Several methods exist by which to assess type A behavior (TAB). Although the videotaped clinical interview is regarded as the "gold standard," self-report measures have also proved useful in assessing TAB in large population studies. The purpose of this study was to examine prospectively the relationship of ...


    pub_type: 杂志文章


    authors: Kawachi I,Sparrow D,Kubzansky LD,Spiro A 3rd,Vokonas PS,Weiss ST

    更新日期:1998-08-04 00:00:00

  • Vacuolar H(+)-ATPase plays a crucial role in growth and phenotypic modulation of myofibroblasts in cultured human saphenous vein.

    abstract:BACKGROUND:The molecular mechanism of neointimal hyperplasia after vein graft surgery remains elusive. Vacuolar H(+)-ATPase (V-ATPase) is involved in intracellular trafficking and may play a crucial role in neointimal cell growth. METHODS AND RESULTS:Cultured human saphenous vein segments developed neointimal formatio...


    pub_type: 杂志文章


    authors: Otani H,Yamamura T,Nakao Y,Hattori R,Fujii H,Ninomiya H,Kido M,Kawaguchi H,Osako M,Imamura H,Ohta T,Ohkuma S

    更新日期:2000-11-07 00:00:00

  • Effect of rate on left ventricular volumes and ejection fraction during chronic ventricular pacing.

    abstract::Resting left ventricular (LV) function was evaluated in 22 patients with permanent ventricular pacemakers. LV ejection fraction and volume indexes were determined by gated blood pool scintigraphy at ventricular pacing rates of 50-100 beats/min. In patients with a normal heart size, increases in pacing rates resulted i...


    pub_type: 杂志文章


    authors: Narahara KA,Blettel ML

    更新日期:1983-02-01 00:00:00

  • Comparative effects of calcium entry-blocking drugs, beta-blocking drugs, and their combination in patients with chronic stable angina.

    abstract::For monotherapy, beta-blockers and calcium-entry blockers are effective and safe antianginal medications. For prophylaxis of myocardial ischemia, a different mechanism of action for each class of drugs is reflected by the different heart rate and rate-pressure product during exercise. In patients who continue to have ...


    pub_type: 临床试验,杂志文章


    authors: Kostuk WJ,Pflugfelder P

    更新日期:1987-06-01 00:00:00

  • Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: a possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone.

    abstract:BACKGROUND:The renin-angiotensin-aldosterone system is involved in the pathogenesis of atherosclerosis, partially because of its pro-oxidative properties. We questioned the effect and mechanisms of action of administration of aldosterone to apolipoprotein E-deficient (E(0)) mice on their macrophages and aorta oxidative...


    pub_type: 杂志文章


    authors: Keidar S,Kaplan M,Pavlotzky E,Coleman R,Hayek T,Hamoud S,Aviram M

    更新日期:2004-05-11 00:00:00

  • RR variability in healthy, middle-aged persons compared with patients with chronic coronary heart disease or recent acute myocardial infarction.

    abstract:BACKGROUND:The purpose of this investigation was to establish normal values of RR variability for middle-aged persons and compare them with values found in patients early and late after myocardial infarction. We hypothesized that presence or absence of coronary heart disease, age, and sex (in this order of importance) ...


    pub_type: 临床试验,杂志文章,多中心研究


    authors: Bigger JT Jr,Fleiss JL,Steinman RC,Rolnitzky LM,Schneider WJ,Stein PK

    更新日期:1995-04-01 00:00:00

  • High-resolution intravascular magnetic resonance imaging: monitoring of plaque formation in heritable hyperlipidemic rabbits.

    abstract:BACKGROUND:The individual makeup of atherosclerotic plaque has been identified as a dominant prognostic factor. With the use of an intravascular magnetic resonance (MR) catheter coil, we evaluated the effectiveness of high-resolution MR in the study of the development of atherosclerotic lesions in heritable hyperlipide...


    pub_type: 杂志文章


    authors: Zimmermann-Paul GG,Quick HH,Vogt P,von Schulthess GK,Kling D,Debatin JF

    更新日期:1999-03-02 00:00:00

  • Toll-like receptor 4-dependent microglial activation mediates spinal cord ischemia-reperfusion injury.

    abstract:BACKGROUND:Paraplegia continues to complicate thoracoabdominal aortic interventions. The elusive mechanism of spinal cord ischemia-reperfusion injury has delayed the development of pharmacological adjuncts. Microglia, the resident macrophages of the central nervous system, can have pathological responses after a variet...


    pub_type: 杂志文章


    authors: Bell MT,Puskas F,Agoston VA,Cleveland JC Jr,Freeman KA,Gamboni F,Herson PS,Meng X,Smith PD,Weyant MJ,Fullerton DA,Reece TB

    更新日期:2013-09-10 00:00:00

  • Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance.

    abstract:BACKGROUND:Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary...


    pub_type: 临床试验,杂志文章


    authors: Jacob G,Shannon JR,Costa F,Furlan R,Biaggioni I,Mosqueda-Garcia R,Robertson RM,Robertson D

    更新日期:1999-04-06 00:00:00

  • Interlesion dependence of the risk for restenosis in patients with coronary stent placement in in multiple lesions.

    abstract:BACKGROUND:Little is known about the behavior with regard to restenosis of multiple lesions within the same patient treated with intracoronary stenting. Our objective was to test the hypothesis that there is an intrapatient dependence of restenosis between lesions. METHODS AND RESULTS:Quantitative analysis was carried...


    pub_type: 杂志文章


    authors: Kastrati A,Schömig A,Elezi S,Schühlen H,Wilhelm M,Dirschinger J

    更新日期:1998-06-23 00:00:00

  • The stunned myocardium: prolonged, postischemic ventricular dysfunction.

    abstract::Myocardial ischemia has, for many decades, been viewed as an all-or-none process that causes myocardial necrosis when prolonged and severe, but whose effects are transient when it is brief or mild. In view of the evidence that the ischemic process may "hit, run and stun," perhaps our thinking about the consequences of...


    pub_type: 杂志文章,评审


    authors: Braunwald E,Kloner RA

    更新日期:1982-12-01 00:00:00