title: Acute myocardial ischemia directly modulates the expression of brain natriuretic peptide at the transcriptional and translational levels via inflammatory cytokines.
abstract: Cardiomyocyte stretching has been reported to be a major trigger for brain natriuretic peptide (BNP) release; however, an increase in circulating BNP is observed in patients with acute myocardial ischemia in the absence of increased left ventricular wall stress or cardiomyocyte stretching. In the present study, to investigate the direct and independent effects of acute myocardial ischemia on BNP expression and its mechanism, we established an in vitro glucose-free ischemia and hypoxia injured model of cultured rat cardiomyotes and proved hypoxia upregulated expressions of interleukin-6(il-6) and BNP. Further treatment with il-6 elicited dose- and time-dependent increases in BNP mRNA and protein expression as well as an upregulation in transforming growth factor-β1 (TGF-β1)/Smad2 expression, which was partially suppressed by a neutralizing antibody. In conclusion, our study showed that acute myocardial ischemia can directly upregulate BNP expression at the translational and transcriptional levels through the action of il-6, and this process is associated with the upregulation of TGF-β1/Smad2 signal path.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Xia
authors.forename: Yi-Yi
authors.initials: YY
authors.lastname: Huang
authors.forename: Yi-Li
authors.initials: YL
authors.lastname: Chen
authors.forename: Sheng-Long
authors.initials: SL
authors.lastname: Chen
authors.forename: Jian-Gui
authors.initials: JG
authors.lastname: He
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D000860:Hypoxia / Q000150:complications; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D017202:Myocardial Ischemia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D012333:RNA, Messenger; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D020097:Natriuretic Peptide, Brain