RETRACTED ARTICLE: Postconditioning promotes the cardiac repair through balancing collagen degradation and synthesis after myocardial infarction in rats

ArticleinArchiv für Kreislaufforschung 108(1):318 · January 2013with24 Reads
DOI: 10.1007/s00395-012-0318-9 · Source: PubMed
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.
    • "The first and the largest group contained early cellular reactions at the onset of MI, including leukocyte transendothelial migration, the Toll-like receptor signaling pathway, the NFκB signaling pathway, the chemokine signaling pathway and apoptosis, suggesting inflammation, immune response and cell apoptosis. The second group displayed cellular responses in the subacute phase, including the TGF-β signalling pathway, which are known to play crucial roles in cardiac repair and remodeling [47, 48]. Finally, several pathways such as alcoholism, glycosaminoglycan degradation, legionellosis, amyotrophic lateral sclerosis and the Notch signaling pathway were enriched in the chronic phase of MI. "
    [Show abstract] [Hide abstract] ABSTRACT: Myocardial infarction (MI) is a serious heart disease and a leading cause of mortality and morbidity worldwide. Although some molecules (genes, miRNAs and transcription factors (TFs)) associated with MI have been studied in a specific pathological context, their dynamic characteristics in gene expressions, biological functions and regulatory interactions in MI progression have not been fully elucidated to date. In the current study, we analyzed time-series RNA expression data from peripheral blood mononuclear cells. We observed that significantly differentially expressed genes were sharply up- or down-regulated in the acute phase of MI, and then changed slowly until the chronic phase. Biological functions involved at each stage of MI were identified. Additionally, dynamic miRNA-TF co-regulatory networks were constructed based on the significantly differentially expressed genes and miRNA-TF co-regulatory motifs, and the dynamic interplay of miRNAs, TFs and target genes were investigated. Finally, a new panel of candidate diagnostic biomarkers (STAT3 and ICAM1) was identified to have discriminatory capability for patients with or without MI, especially the patients with or without recurrent events. The results of the present study not only shed new light on the understanding underlying regulatory mechanisms involved in MI progression, but also contribute to the discovery of true diagnostic biomarkers for MI.
    Full-text · Article · Jul 2016
    • "When the ratio of collagen is disbalanced (i.e., the ratio of type I to type III is increased), decreases the ventricular wall compliance, increases stiffness, and diastolic filling is limited. Finally, myocardial contractile function also becomes limited [17] . Some researchers have found that Salvia miltiorrhiza can reduce myocardial type I collagen, while the flavonoids in Astragalus membranaceus have been found to improve hemodynamics after myocardial infarction,Fig. "
    [Show abstract] [Hide abstract] ABSTRACT: To investigate the ameliorated effects of an extract of Ginkgo biloba extract (GBE) on experimental cardiac remodeling in rats induced by acute cardiac infarction, and further explore the mechanism concentrated on myocardial type I collagen, transforming growth factor beta 1 (TGF-β1), matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9), and provide the experimentaldata for clinical application of GBE. Rats were divided into five groups (n = 20) as following: sham operation group (group A), acute myocardial infarction model group (group B), acute myocardial infarction model + aspirin (10 mg/kg) treatment group (group C), acute myocardial infarction model + captopril (20 mg/kg) treatment group (group D) and acute myocardial infarction model + Ginkgo biloba extract (100 mg/kg) treatment group (group E). The rat acute myocardial infarction model was reproduced by ligaturing the left anterior descending artery excluding the sham operation group which did not ligation only completed the operational process. Each group was further subdivided into treatment regimens lasting 4 weeks and 8 weeks. Immunohistochemistry and real-time polymerase chain reaction (PCR) methods were used to detect the protein expression and mRNA transcriptional levels of rat myocardial TGF-β1, type I collagen, MMP-2 and MMP-9. Compared with group B, regardless of the length of treatment (4 or 8 weeks), the TGF-β1, MMP-2 and MMP-9 mRNA transcriptional levels, and the protein expression levels of type I collagen, MMP-2 and MMP-9 in groups D, C and E were significantly decreased (P < 0.01). Furthermore, the mRNA expression levels of TGF-β1 in groups D, C and E were significantly lower after 8 weeks compared to after 4 weeks (P < 0.01), as were the expression levels of type I collagen in groups D, C and E (P < 0.05). There was no statistically significant difference in the protein expression levels of MMP-2 and MMP-9 between groups E and C. GBE could inhibit experimental rat myocardial remodeling after acute myocardial infarction via reduced transcription of TGF-β1, MMP-2 and MMP-9 genes and by the decreased expression of type I collagen, MMP-2 and MMP-9 proteins in myocardial cells.
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    • "For example, remote conditioning failed to enhance healing, as indicated by changes in tissue hydroxyproline content, after bowel anastomosis surgery in rats (Colak et al. 2007; Holzner et al. 2011). Conversely, post-conditioning was reported to exert a favorable effect on repair at one and six weeks after myocardial infarction in rats by reduction of the area occupied by collagen and an attenuation in expression of collagen types I and III (Wang et al. 2013). However, histological assessment of collagen content was performed with trichrome staining which is known to underestimate collagen content (). "
    [Show abstract] [Hide abstract] ABSTRACT: Thousands of articles have been published on the topic of ischemic conditioning. Nevertheless, relatively little attention has been given to assessment of conditioning's dose-response characteristics. Specifically, the consequences of multiple conditioning epi-sodes, what we will term "hyperconditioning", have seldom been examined. We propose that hyperconditioning warrants investigation because it; (1) may be of clinical impor-tance, (2) could provide insight into conditioning mechanisms, and (3) might result in development of novel models of human disease. The prevalence of angina pectoris and intermittent claudication is sufficiently high and the potential for daily ischemia-reperfu-sion episodes sufficiently large that hyperconditioning is a clinically relevant phenomenon. In basic science, attenuation of conditioning-mediated infarct size reduction found in some studies after hyperconditioning offers a possible means to facilitate further dis-cernment of cardioprotective signaling pathways. Moreover, hyperconditioning's impact extends beyond cytoprotection to tissue structural elements. Several studies demonstrate that hyperconditioning produces collagen injury (primarily fiber breakage). Such struc-tural impairment could have adverse clinical consequences; however, in laboratory stud-ies, selective collagen damage could provide the basis for models of cardiac rupture and dilated cardiomyopathy. Accordingly, we propose that hyperconditioning represents the dark, but potentially illuminating, side of ischemic conditioning -a paradigm that merits attention and prospective evaluation.
    Full-text · Article · Dec 2014
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