Cardioprotective effect of calcineurin inhibition in an animal model of renal disease.

Abstract:

AIMS:Chronic kidney disease is directly associated with cardiovascular complications. Heart remodelling, including fibrosis, hypertrophy, and decreased vascularization, is frequently present in renal diseases. Our objective was to investigate the impact of calcineurin inhibitors (CNI) on cardiac remodelling and function in a rat model of renal disease. METHODS AND RESULTS:Male Sprague Dawley rats were divided into six groups: sham-operated rats, 5/6 nephrectomized rats (Nx) treated with vehicle, CNI (cyclosporine A 5.0 or 7.5, or tacrolimus 0.5 mg/kg/day) or hydralazine (20 mg/kg twice a day) for 14 days, starting on the day of surgery. Creatinine clearance was significantly lower and blood pressure significantly higher in Nx rats when compared with controls. Morphological and echocardiographic analyses revealed increased left ventricular hypertrophy and decreased number of capillaries in Nx rats. Treatment with CNI affected neither the renal function nor the blood pressure, but prevented the development of cardiac hypertrophy and improved vascularization. In addition, regional blood volume improved as confirmed by contrast agent-based echocardiography. Hydralazine treatment did not avoid heart remodelling in this model. Gene expression analysis verified a decrease in hypertrophic genes in the heart of CNI-treated rats, while pro-angiogenic and stem cell-related genes were upregulated. Moreover, mobilization of stem/progenitor cells was increased through manipulation of the CD26/SDF-1 system. CONCLUSION:We conclude from our studies that CNI-treatment significantly prevented cardiac remodelling and improved heart function in Nx rats without affecting renal function and blood pressure. This sheds new light on possible therapeutic strategies for renal patients at high cardiovascular risk.

journal_name

Eur Heart J

journal_title

European heart journal

authors

Di Marco GS,Reuter S,Kentrup D,Ting L,Ting L,Grabner A,Jacobi AM,Pavenstädt H,Baba HA,Tiemann K,Brand M

doi

10.1093/eurheartj/ehq436

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

1935-45

issue

15

eissn

0195-668X

issn

1522-9645

pii

ehq436

journal_volume

32

pub_type

杂志文章
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    更新日期:2017-06-01 00:00:00

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    更新日期:1999-10-01 00:00:00

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    更新日期:1998-12-01 00:00:00

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    更新日期:2006-02-01 00:00:00

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    authors: Monsuez JJ,Vittecoq D,Rosenbaum A,Goujon C,Wolff M,Witchitz S,Modai J

    更新日期:1989-09-01 00:00:00

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    pub_type: 杂志文章

    doi:10.1093/eurheartj/12.suppl_d.108

    authors: Van Houten N,Huber SA

    更新日期:1991-08-01 00:00:00

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    authors: Danchin N,Cuilliere M,Cherrier F

    更新日期:1984-05-01 00:00:00

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    更新日期:2020-03-07 00:00:00

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    更新日期:2004-11-01 00:00:00

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    更新日期:1997-03-01 00:00:00

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    更新日期:2017-04-14 00:00:00

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    pub_type: 杂志文章,多中心研究

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    pub_type: 杂志文章,随机对照试验

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    pub_type: 临床试验,杂志文章

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    更新日期:1996-12-01 00:00:00

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    更新日期:2009-09-01 00:00:00

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    pub_type: 杂志文章

    doi:10.1093/eurheartj/12.7.832

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    更新日期:1991-07-01 00:00:00

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    pub_type: 杂志文章

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    authors: Vliegen HW,van der Laarse A,Cornelisse CJ,Eulderink F

    更新日期:1991-04-01 00:00:00

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    pub_type: 杂志文章

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    pub_type: 杂志文章

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    authors: Cotton JM,Mathur A,Hong Y,Brown AS,Martin JF,Erusalimsky JD

    更新日期:2002-06-01 00:00:00

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    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1093/eurheartj/ehy451

    authors: Byrd JB,Newby DE,Anderson JA,Calverley PMA,Celli BR,Cowans NJ,Crim C,Martinez FJ,Vestbo J,Yates J,Brook RD,SUMMIT Investigators.

    更新日期:2018-09-01 00:00:00

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    pub_type: 杂志文章,评审

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    authors: Underwood SR,Bax JJ,vom Dahl J,Henein MY,Knuuti J,van Rossum AC,Schwarz ER,Vanoverschelde JL,van der Wall EE,Wijns W,Study Group of the European Society of Cardiology.

    更新日期:2004-05-01 00:00:00

  • The significance of myocardial ischaemia and verapamil treatment on the prevalence of supraventricular tachyarrhythmias in patients recovering from acute myocardial infarction. Danish Study Group on Verapamil in Myocardial Infarction.

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    journal_title:European heart journal

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1093/oxfordjournals.eurheartj.a060078

    authors: Jespersen CM,Vaage-Nilsen M,Hansen JF

    更新日期:1992-10-01 00:00:00

  • The short-term effect of intravenous nitroglycerin on haematocrit; an additional benefit in patients with myocardial ischaemia?

    abstract::Organic nitrates exert their effect by direct inhibition of vascular tone, resulting in decreased myocardial oxygen demand and improved oxygen supply. Less well known is the effect of nitrates on blood rheology. To evaluate the haemodiluting effect of intravenous nitroglycerin we studied 70 consecutive patients admitt...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/oxfordjournals.eurheartj.a060362

    authors: Arend SM,Bax JJ,Hermans J,van der Wall EE,Sedney MI

    更新日期:1994-01-01 00:00:00

  • Minor elevations in troponin I are associated with mortality and adverse cardiac events in patients with atrial fibrillation.

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    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehq491

    authors: van den Bos EJ,Constantinescu AA,van Domburg RT,Akin S,Jordaens LJ,Kofflard MJ

    更新日期:2011-03-01 00:00:00

  • Anticoagulation in women with non-valvular atrial fibrillation in the stroke prevention using an oral thrombin inhibitor (SPORTIF) trials.

    abstract:AIMS:The risk of stroke is greater among women with atrial fibrillation (AF) than men. Warfarin protects against stroke, but treatment-related bleeding occurs more often in women than in men. METHODS AND RESULTS:SPORTIF III (open label, n=3410) and V (double-blind, n=3922) included 2257 women with AF and one or more s...

    journal_title:European heart journal

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/eurheartj/ehl103

    authors: Gomberg-Maitland M,Wenger NK,Feyzi J,Lengyel M,Volgman AS,Petersen P,Frison L,Halperin JL

    更新日期:2006-08-01 00:00:00

  • Local hospital vs. core-laboratory interpretation of the admission electrocardiogram in acute coronary syndromes: increased mortality in patients with unrecognized ST-elevation myocardial infarction.

    abstract:AIMS:Previous analyses suggest only modest agreement between local site and core-laboratory (core-lab) electrocardiogram (ECG) interpretation in patients with acute coronary syndromes (ACSs); however, this has not been well examined outside of clinical trial populations. METHODS AND RESULTS:Patients (n = 5277 from 51 ...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究

    doi:10.1093/eurheartj/ehm503

    authors: Vijayaraghavan R,Yan AT,Tan M,Fitchett DH,Georgescu AA,Hassan Q,Langer A,Goodman SG,Canadian Acute Coronary Syndromes Registry Investigators.

    更新日期:2008-01-01 00:00:00