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Pàgina inicial > Articles > Articles publicats > Network-Assisted Systems Biology Analysis of the Mitochondrial Proteome in a Pre-Clinical Model of Ischemia, Revascularization and Post-Conditioning |
Data: | 2022 |
Resum: | Infarct size is the major risk predictor for developing heart failure after an acute myocardial infarction (AMI). The discovery of the conditioning phenomena (i. e. , repetitive brief cycles of ischemia applied either before or after a prolonged ischemic insult) has highlighted the existence of endogenous protective mechanisms of the heart potentially limiting infarct size after revascularization. However, most cardioprotective strategies, aiming at infarct size reduction, have failed in clinical studies. Thus, cardioprotection is an unmet clinical need. In the present study, we took a network-assisted systems biology approach to explore the mitochondrial proteomic signature of the myocardium after ischemia, ischemia with direct revascularization, and ischemia with re-establishment of blood flow by postconditioning in a swine model of AMI. Furthermore, network extension with the ENCODE project human regulatory data allowed the prediction of potential transcription factors at play in the response to post-conditioning of the myocardium. Collectively, our results identify cardiac metabolism as a driver of cardioprotection, highlighting a dual role for post-conditioning promoting metabolic reprogramming of the myocardium, and a protective response mediated by VDAC2 and DJ-1 in the mitochondria. |
Ajuts: | Agencia Estatal de Investigación SAF-2016-76819-R Agencia Estatal de Investigación PID2019-107160RB-I00 Agencia Estatal de Investigación RETOS-PID2019-107160RB Agencia Estatal de Investigación PGC2018-094025-B-I00 Agencia Estatal de Investigación BES-2017-081378 Instituto de Salud Carlos III ERA-CVD JTC 2020-023/AC 209-00054 Instituto de Salud Carlos III FIS PI19/01687 |
Nota: | Altres ajuts: Ministerio de Ciencia e Innovación; Fundación de Investigación Cardiovascular-Fundación Jesús Serra. |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Post-conditioning ; Ischemia ; Cardioprotection ; Mitochondria ; Proteomics ; Network biology |
Publicat a: | International journal of molecular sciences, Vol. 23 Núm. 4 (February 2022) , p. 2087, ISSN 1422-0067 |
15 p, 1.8 MB |