Myocardial ischemic postconditioning against ischemia-reperfusion is impaired in ob/ob mice. - Archive ouverte HAL Access content directly
Journal Articles AJP - Heart and Circulatory Physiology Year : 2008

Myocardial ischemic postconditioning against ischemia-reperfusion is impaired in ob/ob mice.

(1, 2) , (1, 2) , (3) , (1, 2) , (1, 2, 4) , (1, 2, 4)
1
2
3
4

Abstract

Ischemic postconditioning (IPCD) significantly reduces infarct size in healthy animals and protects the human heart. Because obesity is a major risk factor of cardiovascular diseases, the effects of IPCD were investigated in 8- to 10-wk-old leptin-deficient obese (ob/ob) mice and compared with wild-type C57BL/6J (WT) mice. All animals underwent 30 min of coronary artery occlusion followed by 24 h of reperfusion associated or not with IPCD (6 cycles of 10-s occlusion, 10-s reperfusion). Additional mice were killed at 10 min of reperfusion for Western blotting. IPCD reduced infarct size by 58% in WT mice (33 +/- 1% vs. 14 +/- 3% for control and IPCD, respectively, P < 0.05) but failed to induce cardioprotection in ob/ob mice (53 +/- 4% vs. 56 +/- 5% for control and IPCD, respectively). In WT mice, IPCD significantly increased the phosphorylation of Akt (+77%), ERK1/2 (+41%), and their common target p70S6K1 (+153% at Thr389 and +57% at Thr421/Ser424). In addition, the phosphorylated AMP-activated protein kinase (AMPK)-to-total AMPK ratio was also increased by IPCD in WT mice (+64%, P < 0.05). This was accompanied by decreases in phosphatase and tensin homolog deleted on chromosome 10 (PTEN), MAP kinase phosphatase (MKP)-3, and protein phosphatase (PP)2C levels. In contrast, IPCD failed to increase the phosphorylation state of all these kinases in ob/ob mice, and the level of the three phosphatases was significantly increased. Thus, although IPCD reduces myocardial infarct size in healthy animals, its cardioprotective effect vanishes with obesity. The lack of enhanced phosphorylation by IPCD of Akt, ERK1/2, p70S6K1, and AMPK might partly explain the loss of cardioprotection in this experimental model of obese mice.
Fichier principal
Vignette du fichier
inserm-00335256_edited.pdf (1.21 Mo) Télécharger le fichier
Vignette du fichier
ob-total-pdf-format.pdf (445.72 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Loading...

Dates and versions

inserm-00335256 , version 1 (10-09-2009)

Identifiers

Cite

Omar Bouhidel, Sandrine Pons, Richard Souktani, Roland Zini, Alain Berdeaux, et al.. Myocardial ischemic postconditioning against ischemia-reperfusion is impaired in ob/ob mice.. AJP - Heart and Circulatory Physiology, 2008, 295 (4), pp.H1580-6. ⟨10.1152/ajpheart.00379.2008⟩. ⟨inserm-00335256⟩

Collections

INSERM IMRB UPEC
168 View
466 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More