Benefit of SERCA2a gene transfer to vascular endothelial and smooth muscle cells: a new aspect in therapy of cardiovascular diseases.
Benefit of SERCA2a gene transfer to vascular endothelial and smooth muscle cells: a new aspect in therapy of cardiovascular diseases.
复制标题
SERCA2A基因转移到血管内皮和平滑肌细胞的益处：心血管疾病治疗的新方面。
DOI：
10.2174/1570161111311040010
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发表时间：
2013-07
影响因子：
4.5
通讯作者：
Bobe R
中科院分区：
文献类型：
--
作者：
Lipskaia L;Hadri L;Lopez JJ;Hajjar RJ;Bobe R
尽管心血管健康和临床护理沿着发病率和死亡率的显著下降，但心血管疾病仍然是发达国家死亡和残疾的主要原因。最终需要新的治疗方法，不仅针对系统性功能障碍，而且针对因果性功能障碍，为复杂心血管疾病的治疗提供有价值的替代方案。在心力衰竭中，目前有许多试验已经完成或正在进行中，靶向心力衰竭背景下的肌浆网钙ATP酶泵（SERCA 2a）基因转移。最近，完成了一项2期试验，证明了腺相关病毒1型/SERCA 2a基因转移在晚期心力衰竭中的安全性和建议的益处，支持更大规模的验证性试验。实验和临床数据表明，当通过灌注施用时，携带SERCA 2a的病毒载体还可以使血管内皮细胞和平滑肌细胞（EC和SMC）增殖，从而提高基因治疗的临床益处。事实上，在理解血管功能障碍的分子基础方面的最新进展指向来自患有心脏病或具有心血管风险因素（如糖尿病、高胆固醇血症、冠状动脉疾病以及其他病症（如肺动脉高压））的患者和临床前模型的血管EC和SMC中肌浆网Ca 2+摄取的减少和Ca 2+循环的损害。近年来，一些研究已经确定，基于SERCA 2a基因的治疗可能是治疗血管功能障碍的有效选择。本文综述了SERCA 2a基因转染对血管EC和SMC的有益作用。
Despite the great progress in cardiovascular health and clinical care along with marked decline in morbidity and mortality, cardiovascular diseases remain the leading causes of death and disability in the developed world. New therapeutic approaches, targeting not only systematic but also causal dysfunction, are ultimately needed to provide a valuable alternative for treatment of complex cardiovascular diseases. In heart failure, there are currently a number of trials that have been either completed or are ongoing targeting the sarcoplasmic reticulum calcium ATPase pump (SERCA2a) gene transfer in the context of heart failure. Recently, a phase 2 trial was completed, demonstrating safety and suggested benefit of adeno-associated virus type 1/SERCA2a gene transfer in advanced heart failure, supporting larger confirmatory trials. The experimental and clinical data suggest that, when administrated through perfusion, virus vector carrying SERCA2a can also transduce vascular endothelial and smooth muscle cells (EC and SMC) thereby improving the clinical benefit of gene therapy. Indeed, recent advances in understanding the molecular basis of vascular dysfunction point towards a reduction of sarcoplasmic reticulum Ca2+ uptake and an impairment of Ca2+ cycling in vascular EC and SMC from patients and preclinical models with cardiac diseases or with cardiovascular risk factors such as diabetes, hypercho-lesterolemia, coronary artery diseases, as well as other conditions such as pulmonary hypertension. In recent years, several studies have established that SERCA2a gene-based therapy could be an efficient option to treat vascular dysfunction. This review focuses on the recent finding showing the beneficial effects of SERCA2a gene transfer in vascular EC and SMC.