17-beta-Estradiol decreases p38 MAPK-mediated myocardial inflammation and dysfunction following acute ischemia.
Understanding the inflammatory response to myocardial ischemia is an important part of achieving the elusive clinical goal of perfect myocardial protection. While it is established that estrogen affects the chronic inflammatory processes of coronary atherosclerosis, the effects of estrogen on acute myocardial proinflammatory signaling are unknown. To study this, myocardial ischemia and reperfusion was performed in rat hearts from normal adult males, normal adult females, ovariectomized (OVX) females, males supplemented with E2, and OVX females supplemented with E2. Following reperfusion, homogenized hearts were analyzed for TNF-alpha, IL-1beta, and IL-6 gene and protein expression, p38 MAPK activation, and the apoptosis-related proteins caspase-3 and Bcl-2. Hearts from proestrus females demonstrated significantly better post-ischemic functional recovery than males. E2 supplementation to males and OVX females improved post-ischemic myocardial functional recovery, reduced the production of TNF-alpha, IL-1beta and IL-6, and decreased the activation of p38 MAPK and caspase-3 when compared to their untreated counterparts. These results suggest that the effect of estrogen on cardioprotection against myocardial I/R may be attributed to its anti-inflammatory and anti-apoptotic properties. Further understanding of these mechanisms may allow therapeutic manipulation of sex hormones in the treatment of acute ischemic injury.
Wang
Meijing
M
Department of Cardiothoracic Surgery, Indiana University Medical Center, 545 Barnhill Drive, Emerson Hall 215, Indianapolis, IN 46202, USA.
Tsai
Ben M
BM
Reiger
Karen M
KM
Brown
John W
JW
Meldrum
Daniel R
DR
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D004958:Estradiol / Q000502:physiology*; D005260:Female; D007249:Inflammation / Q000201:enzymology*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D007375:Interleukin-1; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3