UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

The novel adipocytokine visfatin exerts direct cardioprotective effects

Lim, SY; Davidson, SM; Paramanathan, AJ; Smith, CCT; Yellon, DM; Hausenloy, DJ; (2008) The novel adipocytokine visfatin exerts direct cardioprotective effects. J CELL MOL MED , 12 (4) 1395 - 1403. 10.1111/j.1582-4934.2008.00332.x. Gold open access

Abstract

Visfatin is an adipocytokine capable of mimicking the glucose-lowering effects of insulin and activating the pro-survival kinases phosphatidylinositol-3-OH kinase (PI3K)-protein kinase B (Akt) and mitogen-activated protein kinase kinase 1 and 2 (MEK1/2)-extracellular signal-regulated kinase 1 and 2 (Erk 1/2). Experimental studies have demonstrated that the activation of these kinases confers cardioprotection through the inhibition of the mitochondrial permeability transition pore (mPTP). Whether visfatin is capable of exerting direct cardioprotective effects through these mechanisms is unknown and is the subject of the current study. Anaesthetized C57BL/6 male mice were subjected to in situ 30 min. of regional myocardial ischaemia and 120 min. of reperfusion. The administration of an intravenous bolus of visfatin (5 x 10(-6) mu mol) at the time of myocardial reperfusion reduced the myocardial infarct size from 46.1 +/- 4.1% in control hearts to 27.3 +/- 4.0% (n >= 6/group, P < 0.05), an effect that was blocked by the PI3K inhibitor, wortmannin, and the MEK1/2 inhibitor, U0126 (48.8 +/- 5.5% and 45.9 +/- 8.4%, respectively, versus 27.3 +/- 4.0% with visfatin; n >= 6/group, P < 0.05). In murine ventricular cardiomyocytes subjected to 30 min. of hypoxia followed by 30 min. of reoxygenation, visfatin (100 ng/ml), administered at the time of reoxygenation, reduced the cell death from 65.2 +/- 4.6% in control to 49.2 +/- 3.7% (n > 200 cells/group, P < 0.05), an effect that was abrogated by wortmannin and U0126 (68.1 +/- 5.2% and 59.7 +/- 6.2%, respectively; n > 200 cells/group, P > 0.05). Finally, the treatment of murine ventricular cardiomyocytes with visfatin (100 ng/ml) delayed the opening of the mPTP induced by oxidative stress from 81.2 +/- 4 sec. in control to 120 +/- 7 sec. (n > 20 cells/group, P < 0.05) in a PI3K- and MEK1/2-dependent manner. We report that the adipocytokine, visfatin, is capable of reducing myocardial injury when administered at the time of myocardial reperfusion in both the in situ murine heart and the isolated murine cardiomyocytes. The mechanism appears to involve the PI3K and MEK1/2 pathways and the mPTP.

Type: Article
Title: The novel adipocytokine visfatin exerts direct cardioprotective effects
Open access status: An open access publication
DOI: 10.1111/j.1582-4934.2008.00332.x
Publisher version: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC29056...
Keywords: visfatin, ischaemia, reperfusion, cardioprotection, COLONY-ENHANCING FACTOR, PERMEABILITY TRANSITION PORE, ISCHEMIA-REPERFUSION INJURY, TYPE-2 DIABETES-MELLITUS, METABOLIC SYNDROME, NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE, CARDIOVASCULAR-DISEASE, MYOCARDIAL-INFARCTION, WEIGHT-LOSS, EXPRESSION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/179357
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item