Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 44, Issue 1, Pages 123-130Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2007.10.003
Keywords
caveolae; caveolin-3; cardiac protection; volatile anesthetics; ischemia/reperfusion injury
Categories
Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL081400, P01HL066941] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL081400, R01 HL081400-01A2, R01 HL081400, P01 HL066941, HL66941] Funding Source: Medline
Ask authors/readers for more resources
Volatile anesthetics protect the heart from ischemia/reperfusion injury but the mechanisms for this protection are poorly understood. Caveolae, sarcolemmal invaginations, and caveolins, scaffolding proteins in caveolae, localize molecules involved in cardiac protection. We tested the hypothesis that caveolae and caveolins are essential for volatile anesthetic-induced cardiac protection using cardiac myocytes (CMs) from adult rats and in vivo studies in caveolin-3 knockout mice (Cav-3(-/-)). We incubated CM with methyl-beta-cyclodextrin (M beta CD) or colchicine to disrupt caveolae formation, and then exposed the myocytes to the volatile anesthetic isoflurane (30 min, 1.4%), followed by simulated ischemia/reperfusion (SI/R). Isoflurane protected CM from SUR [23.2 +/- 1.6% vs. 71.0 +/- 5.8% cell death (assessed by trypan blue exclusion), P<0.001] but this protection was abolished by M beta CD or colchicine (84.9 +/- 5.5% and 64.5 +/- 6.1% cell death, P<0.001). Membrane fractionation by sucrose density gradient centrifugation of CM treated with M beta CD or colchicine revealed that buoyant (caveolae-enriched) fractions bad decreased phosphocaveolin-1 and caveolin-3 compared to control CM. Cardiac protection in vivo was assessed by measurement of infarct size relative to the area at risk and cardiac troponin levels. Isoflurane-induced a reduction in infarct size and cardiac troponin relative to control (infarct size: 26.5% +/- 2.6% vs. 45.3% +/- 5.4%, P<0.01; troponin: 27.7 +/- 4.4 vs. 77.7 +/- 11.8 ng/ml, P<0.05). Isoflurane-induced cardiac protection was abolished in Cav-3(-/-) mice (infarct size: 53.4% +/- 6.1% vs. 53.2% +/- 3.5%, P<0.01; troponin: 102.1 +/- 22.3 vs. 105.9 +/- 8.2 ng/ml, P<0.01). Isoflurane-induced cardiac protection is thus dependent on the presence of caveolae and the expression of caveolin-3. We conclude that caveolae and caveolin-3 are critical for volatile anesthetic- induced protection of the heart from ischemia/reperfusion injury. (C) 2007 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available