Myocardial infarction induces endothelial dysfunction with independence of cardiovascular risk factors.
作者信息
Jimenez-Trinidad Francisco Rafael, Solanes Núria, Arrieta Marta, Llonch Blanca, Roqué Mercè, Freixa Xavier, Brugaletta Salvatore, Ortega-Paz Luis, Rodríguez Juan José, Cepas-Guillen Pedro, Vilhaur Gemma, Sabaté Manel, Dantas Ana Paula, Tura-Ceide Olga, Rigol Montserrat
机构信息
Cardiology Department, Institut Clinic Cardiovascular (ICCV), Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL, USA.
出版信息
Angiogenesis. 2025 Sep 30;28(4):52. doi: 10.1007/s10456-025-10006-8.
AIMS
Endothelial dysfunction and impaired angiogenesis are hallmarks of ischemic heart disease and critical determinants of adverse cardiovascular outcomes after myocardial infarction (MI). While conventional cardiovascular risk factors (CVRFs) are known contributors, the specific role of MI itself triggering endothelial dysfunction remains unclear. This study aims to assess the direct impact of MI on endothelial function, independent of cardiovascular risk factors, using human and porcine endothelial colony-forming cells (ECFCs) as a surrogate cellular model.
METHODS AND RESULTS
Human ECFCs (hECFCs) were isolated from the peripheral blood of healthy volunteers (Control-hECFCs, n = 6), patients immediately after MI (AMI-hECFCs, n = 6), and patients 6 months after MI (CMI-hECFCs, n = 6). To evaluate the direct effect of MI independently of CVRFs, a porcine model was used: healthy pigs (n = 6) underwent 90 min of myocardial ischemia by coronary balloon occlusion followed by reperfusion. Porcine ECFCs (pECFCs) were isolated before MI (Control-pECFCs) and one month after MI (CMI-pECFCs, n = 6). In vitro, CMI-hECFCs and CMI-pECFCs had delayed colony formation, whereas AMI-hECFCs did not. Morphological alterations were observed in AMI-hECFCs and CMI-hECFCs (area and shape), while only shape changes were found in CMI-pECFCs. Senescence was increased in AMI-hECFCs and CMI-hECFCs, but not in CMI-pECFCs. Elevated oxidative stress was only detected in CMI-hECFCs. Functional angiogenic and proliferative capacities were reduced in AMI-hECFCs, CMI-hECFCs and CMI-pECFCs; however, only CMI-hECFCs and CMI-pECFCs displayed impaired migration. Molecular analysis showed overactivation of the MSK2/MKK3/p53 signalling axis in dysfunctional ECFCs, while synergistic inhibition of the axis partially restored ECFC function.
CONCLUSIONS
MI induces sustained ECFC dysfunction independently of cardiovascular risk factors. Targeting the MSK2/MKK3/p53 pathway may be a promising therapeutic strategy to restore endothelial function and improve angiogenesis after MI.
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