title: Postconditioning promotes the cardiac repair through balancing collagen degradation and synthesis after myocardial infarction in rats.
abstract: Postconditioning (Postcon) reduces infarct size. However, its role in modulation of cardiac repair after infarction is uncertain. This study tested the hypothesis that Postcon inhibits adverse cardiac repair by reducing degradation of extracellular matrix (ECM) and synthesis of collagens via modulating matrix metalloproteinase (MMP) activity and transforming growth factor (TGF) β1/Smad signaling pathway. Sprague-Dawley rats were subjected to 45 min ischemia followed by 3 h, 7 or 42 days of reperfusion, respectively. In acute studies, four cycles of 10/10 s Postcon significantly reduced infarct size, which was blocked by administration of a mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate (5-HD) at reperfusion. In chronic studies, Postcon inhibited MMP activity and preserved ECM from degradation as evidenced by reduced extent of collagen-rich scar and increased mass of viable myocardium. Along with a reduction in collagen synthesis and fibrosis, Postcon significantly down-regulated expression of TGFβ1 and phospho-Smad2/3, and up-regulated Smad7 as compared to the control, consistent with a reduction in the population of α-smooth muscle actin expressing myofibroblasts within the infarcted myocardium. At 42 days of reperfusion, echocardiography showed significant improvements in left ventricular end-diastolic volume and ejection fraction. The wall thickness of the infarcted middle anterior septum in the Postcon was also significantly greater than that in the control. The beneficial effects of Postcon on cardiac repair were comparable to preconditioning and still evident after a blockade with 5-HD. These data suggest that Postcon is effective to promote cardiac repair and preserve cardiac function; protection is potentially mediated by inhibiting ECM degradation and collagen synthesis.
authors.affiliation: Cardiovascular Research Laboratory, Mercer University School of Medicine, Savannah, GA 31404, USA.
authors.forename: Zhang-Feng
authors.initials: ZF
authors.lastname: Wang
authors.forename: Ning-Ping
authors.initials: NP
authors.lastname: Wang
authors.forename: Suzanna
authors.initials: S
authors.lastname: Harmouche
authors.forename: Tiji
authors.initials: T
authors.lastname: Philip
authors.forename: Xue-Fen
authors.initials: XF
authors.lastname: Pang
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003652:Decanoic Acids / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D006880:Hydroxy Acids / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D057775:Ischemic Postconditioning; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051785:Smad Proteins / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D016277:Ventricular Function, Left
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D015850:Interleukin-6; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C052853:5-hydroxydecanoic acid; D003094:Collagen; D020782:Matrix Metalloproteinases