Differential regulation of cardiac heme oxygenase-1 and vascular endothelial growth factor mRNA expressions by hemin, heavy metals, heat shock and anoxia.

Increasing attention has been paid to the effects of hypoxia, heavy metals and heat shocks on gene expression and to the similarities in their actions. This paper compares mRNA levels of two putative hypoxia, heavy metal and heat shock sensitive genes: heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) in myocyte-enriched cultures of neonatal rat heart cells. HO-1 mRNA expression is stimulated by hemin, Cd2+, Co2+ and heat shocks but not by Ni2+ or Mn2+. It is stimulated by long (13h) but not by short (4h) periods of anoxia. Conversely, VEGF mRNA expression is stimulated by short as well as long periods of anoxia, by Cd2+, Co2+, Ni2+ and Mn2+ but not by hemin or heat shocks. The results suggest that heavy metals, anoxia and heat shocks exert their effects on VEGF and HO-1 mRNA expression through separate though potentially overlapping mechanisms. Increased expressions of HO-1 and VEGF may be both cardioprotective under hypoxic/ischemic conditions.