Cholesterol diet leads to attenuation of ischemic preconditioning-induced cardiac protection: The role of connexin 43

Anikó Görbe, Zoltán V. Varga, Krisztina Kupai, Péter Bencsik, Gabriella F. Kocsis, Tamás Csont, Kerstin Boengler, Rainer Schulz, Péter Ferdinandy

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Cardioprotection by ischemic preconditioning (IP) was abolished in connexin 43 (Cx43)-deficient mice due to loss of Cx43 located in mitochondria rather than at the sarcolemma. IP is lost in hyperlipidemic rat hearts as well. Since changes in mitochondrial Cx43 in hyperlipidemia have not yet been analyzed, we determined total and mitochondrial Cx43 levels in male Wistar rats fed a laboratory chow enriched with 2% cholesterol or normal chow for 12 wk. Hearts were isolated and perfused according to Langendorff. After a 10-min perfusion, myocardial tissue cholesterol, superoxide, and nitrotyrosine contents were measured and Cx43 content in whole heart homogenate and a mitochondrial fraction determined. In the cholesterol-fed group, tissue cholesterol and superoxide formation was increased (P <.05), while total Cx43 content remained unchanged. Mitochondrial total and dephosphorylated Cx43 content decreased. Hearts were subjected to an IP protocol (3 × 5 min ischemia-reperfusion) or time-matched aerobic perfusion followed by 30-min global ischemia and 5-min reperfusion. IP reduced infarct size in normal but not in cholesterolfed rats. At 5-min reperfusion following 30-min global ischemia, the total and dephosphorylated mitochondrial Cx43 content was increased, which was abolished by IP in both normal and high-cholesterol diet. In conclusion, loss of cardioprotection by IP in hyperlipidemia is associated with a redistribution of both sarcolemmal and mitochondrial Cx43.

Original languageEnglish
Pages (from-to)H1907-H1913
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number5
DOIs
Publication statusPublished - May 1 2011

Keywords

  • Mitochondria
  • Superoxide

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Cholesterol diet leads to attenuation of ischemic preconditioning-induced cardiac protection: The role of connexin 43'. Together they form a unique fingerprint.

  • Cite this