Gianluca Campo1, Giampaolo Morciano2, Rita Pavasini3, Massimo Bonora2, Luigi Sbano2, Simone Biscaglia3, Matteo Bovolenta4, Mirko Pinotti4, Silvia Punzetti3, Paola Rizzo5, Giorgio Aquila5, Carlotta Giorgi2, Roberto Ferrari6, Paolo Pinton2. 1. Cardiovascular Institute, Azienda Ospedaliero-Universitaria S.Anna, Cona, FE, Italy; Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy. Electronic address: cmpglc@unife.it. 2. Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy. 3. Cardiovascular Institute, Azienda Ospedaliero-Universitaria S.Anna, Cona, FE, Italy. 4. Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy. 5. Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy. 6. Cardiovascular Institute, Azienda Ospedaliero-Universitaria S.Anna, Cona, FE, Italy; Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy; Maria Cecilia Hospital, GVM Care & Research, E.S: Health Science Foundation, Cotignola, Italy.
Abstract
BACKGROUND: Recent studies in cell cultures hypothesized that the long-sought molecular pore of the mitochondrial permeability transition pore could be the Fo ATP synthase C subunit (Csub). We assessed Csub in patients with ST-segment elevation myocardial infarction (STEMI) and if it is associated with surrogate endpoints of myocardial reperfusion. METHODS: We enrolled 158 first-time acute anterior STEMI treated with successful percutaneous coronary intervention (PCI). Csub was measured, after the procedure, in serum by ELISA. Csub values were related to thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG), TIMI frame count (TFC), ST-segment resolution and cardiac marker release. Echocardiography and clinical outcome were recorded at 6months. RESULTS: Csub was detectable in serum and it was not normally distributed (6.3% [4-9.3%]). Csub values were higher in patients with poor values of TMPG and TFC (p=0.002 and p=0.001, respectively). Csub values were higher in patients with absent or partial ST-segment resolution as compared to those with complete ST-segment resolution (p<0.0001 and p=0.003, respectively). After adjustment for potential confounding factors, Csub emerged as an independent determinant of absent ST-segment resolution (HR 1.8, 95% CI 1.5-2.3, p=0.007), TMPG 0-1 (HR 1.7, 95% CI 1.3-2.5, p=0.01) and TFC above the median value (HR 1.5, 95% CI 1.3-2.1, p=0.03). Left ventricle ejection fraction, wall motion score index and cumulative incidence of death and heart failure were worse in patients with elevated Csub. CONCLUSIONS: Our study is the first evidence that Csub is detectable in STEMI patients and that it is significantly related to several surrogate markers of myocardial reperfusion.
BACKGROUND: Recent studies in cell cultures hypothesized that the long-sought molecular pore of the mitochondrial permeability transition pore could be the Fo ATP synthase C subunit (Csub). We assessed Csub in patients with ST-segment elevation myocardial infarction (STEMI) and if it is associated with surrogate endpoints of myocardial reperfusion. METHODS: We enrolled 158 first-time acute anterior STEMI treated with successful percutaneous coronary intervention (PCI). Csub was measured, after the procedure, in serum by ELISA. Csub values were related to thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG), TIMI frame count (TFC), ST-segment resolution and cardiac marker release. Echocardiography and clinical outcome were recorded at 6months. RESULTS: Csub was detectable in serum and it was not normally distributed (6.3% [4-9.3%]). Csub values were higher in patients with poor values of TMPG and TFC (p=0.002 and p=0.001, respectively). Csub values were higher in patients with absent or partial ST-segment resolution as compared to those with complete ST-segment resolution (p<0.0001 and p=0.003, respectively). After adjustment for potential confounding factors, Csub emerged as an independent determinant of absent ST-segment resolution (HR 1.8, 95% CI 1.5-2.3, p=0.007), TMPG 0-1 (HR 1.7, 95% CI 1.3-2.5, p=0.01) and TFC above the median value (HR 1.5, 95% CI 1.3-2.1, p=0.03). Left ventricle ejection fraction, wall motion score index and cumulative incidence of death and heart failure were worse in patients with elevated Csub. CONCLUSIONS: Our study is the first evidence that Csub is detectable in STEMI patients and that it is significantly related to several surrogate markers of myocardial reperfusion.