Bär Christian, Bernardes de Jesus Bruno, Serrano Rosa, Tejera Agueda, Ayuso Eduard, Jimenez Veronica, Formentini Ivan, Bobadilla Maria, Mizrahi Jacques, de Martino Alba, Gomez Gonzalo, Pisano David, Mulero Francisca, Wollert Kai C, Bosch Fatima, Blasco Maria A
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Centre of Animal Biotechnology and Gene Therapy (CBATEG), Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat Autónoma de Barcelona, E-08193 Bellaterra, Spain.
Nat Commun. 2014 Dec 18;5:5863. doi: 10.1038/ncomms6863.
Coronary heart disease is one of the main causes of death in the developed world, and treatment success remains modest, with high mortality rates within 1 year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases, including heart disease. Here we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared with controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work suggests telomerase activation could be a therapeutic strategy to prevent heart failure after MI.
冠心病是发达国家主要的死亡原因之一,治疗成功率仍然不高,心肌梗死(MI)后1年内死亡率很高。因此,需要新的治疗靶点和有效的治疗方法。短端粒是包括心脏病在内的与年龄相关疾病的危险因素。在此,我们探讨了端粒酶(Tert)激活在预防成年小鼠心肌梗死后心力衰竭中的潜力。我们使用腺相关病毒进行心脏特异性Tert表达。我们发现,心肌梗死后,与对照组相比,表达Tert的心脏心脏扩张减弱,心室功能改善,梗死瘢痕较小,小鼠存活率提高了17%。此外,Tert治疗导致端粒延长,Ki67和pH3阳性心肌细胞数量增加,基因表达转向新生小鼠的再生特征。我们的研究表明,端粒酶激活可能是预防心肌梗死后心力衰竭的一种治疗策略。