Gene expression after short periods of coronary occlusion

Mol Cell Biochem. 1998 Sep;186(1-2):43-51.

Abstract

Brief periods of coronary occlusion render the affected myocardium more tolerant to the otherwise devastating effects of long coronary occlusion. Besides this phenomena, called ischemic preconditioning, short periods of ischemia cause a regional dysfunction, namely myocardial stunning. The molecular mechanisms of both syndromes are not very well understood. We therefore investigated the expression of genes which may be involved in cardioprotection or repair processes. Using our porcine model of ischemia and reperfusion we were able to show an induction of genes coding for transcription factors (proto-oncogenes), for proteins involved in repair processes (heat shock genes), for proteins implicated in the calcium homeostasis (calcium-handling genes) and for growth factors. We could show that the increased mRNA levels are due to an enhanced transcriptional activity and not to a prolonged half-life of the transcripts. The angiogenic growth factor vascular endothelial growth factor (VEGF) represents an exception. It exhibits--in addition to a HIF-motif (Hypoxia Inducible Factor) in its promoter/enhancer--a protein binding region in its 3' UTR which when occupied renders the mRNA more stable. However to what extent the expression of the distinct genes contributes to the cardioprotective effect of ischemic preconditioning or myocardial stunning can only be presumed. Increased mRNA stability can be confered via adenosine which is produced during ischemia by ATP-breakdown. The demasking of unknown genes--via differential display reverse transcription polymerase chain reaction (DDRT-PCR)--should provide a more comprehensive view of the mechanisms underlying both processes.

MeSH terms

  • Animals
  • Calcium-Binding Proteins / genetics
  • Constriction, Pathologic
  • Coronary Vessels
  • Disease Models, Animal
  • Female
  • Gene Expression*
  • Growth Substances / genetics
  • Heat-Shock Proteins / genetics
  • Ischemic Preconditioning, Myocardial
  • Male
  • Myocardial Reperfusion Injury / genetics*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Stunning / genetics
  • Myocardial Stunning / metabolism
  • Proto-Oncogenes
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Swine
  • Transcription Factors / genetics

Substances

  • Calcium-Binding Proteins
  • Growth Substances
  • Heat-Shock Proteins
  • RNA, Messenger
  • Transcription Factors