期刊
CARDIOVASCULAR RESEARCH
卷 88, 期 2, 页码 304-313出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvq183
关键词
Annexin A5; Mitochondrial dysfunction; Heart failure; Resynchronization; Ventricular dyssynchrony
资金
- Fondo de Investigaciones Sanitarias, Ministry of Health, Spain [PS09/02247]
- Direccion General de Investigacion [SAF2005-06643-C03-01]
- Ministry of Education and Science, Spain
- Red Tematica de Investigacion de las Enfermedades Cardiovasculares, RECAVA, Ministry of Health, Spain [RD 06/0014/0008]
- European Union Network of Excellence on Integrated Genomics, Clinical Research and Care in Hypertension, Ingenious HyperCare [LSHM-CT-2006-037093]
- FIMA
- UTE-CIMA project, Pamplona, Spain
Cardiac resynchronization therapy (CRT) diminishes cardiac apoptosis and improves systolic function in heart failure (HF) patients with ventricular dyssynchrony. Plasma annexin A5 (AnxA5), a protein related to cellular damage, is associated with systolic dysfunction. We investigated whether the response to CRT is associated with plasma AnxA5. We also studied AnxA5 overexpression effects in HL-1 cardiomyocytes. AnxA5 ELISA was performed in plasma from 57 patients with HF and ventricular dyssynchrony at baseline and after 1 year of CRT. Patients were categorized as responders if they presented both a reduction in left ventricular (LV) end-systolic volume index (LVESVi) > 10% and an increase in LV ejection fraction (LVEF) > 10%. HL-1 cells were transfected with human AnxA5 cDNA, and AnxA5, PKC, Akt, p38MAPK, Bcl-2, mitochondrial integrity, caspase-3, and ATP were assessed. At baseline, an increased plasma AnxA5 level was associated with decreased LVEF and increased LVEDVi values (P < 0.05). No differences in baseline AnxA5 were observed between responders and non-responders. After CRT, AnxA5 decreased (P = 0.001) in responders but remained unchanged in non-responders. Final values of AnxA5 were independently associated with LVEF (r = -0.387, P = 0.003) and LVESVi (r = 0.403, P = 0.004) in all patients. Compared with control cells, AnxA5-transfected cells exhibited AnxA5 overexpression, decreased PKC and Akt and increased p38MAPK and Bcl-2 phosphorylation, loss of mitochondrial integrity, caspase-3 activation, and decreased ATP. CRT-induced LV reverse remodelling is associated with reduction in plasma AnxA5. The excess of AnxA5 is detrimental for HL-1 cardiomyocytes. Collectively, these data suggest that the beneficial effects of CRT might be related to an AnxA5 decrease.
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