Magenta Alessandra, Lorde Reggio, Syed Sunayana Begum, Capogrossi Maurizio C, Puca Annibale, Madeddu Paolo
Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Rome, Italy.
Bristol Medical School (Translational Health Sciences), Bristol Heart Institute, University of Bristol, Bristol, UK.
Vasc Biol. 2020 Jan 16;2(1):R45-R58. doi: 10.1530/VB-19-0029. eCollection 2020.
Regenerative medicine is a new therapeutic modality that aims to mend tissue damage by encouraging the reconstitution of physiological integrity. It represents an advancement over conventional therapies that allow reducing the damage but result in disease chronicization. Age-related decline in spontaneous capacity of repair, especially in organs like the heart that have very limited proliferative capacity, contributes in reducing the benefit of conventional therapy. ncRNAs are emerging as key epigenetic regulators of cardiovascular regeneration. Inhibition or replacement of miRNAs may offer reparative solutions to cardiovascular disease. The first part of this review article is devoted to illustrating novel therapies emerging from research on miRNAs. In the second part, we develop new therapeutic concepts emerging from genetics of longevity. Prolonged survival, as in supercentenarians, denotes an exceptional capacity to repair and cope with risk factors and diseases. These characteristics are shared with offspring, suggesting that the regenerative phenotype is heritable. New evidence indicates that genetic traits responsible for prolongation of health span in humans can be passed to and benefit the outcomes of animal models of cardiovascular disease. Genetic studies have also focused on determinants of accelerated senescence and related druggable targets. Evolutionary genetics assessing the genetic basis of adaptation and comparing successful and unsuccessful genetic changes in response to selection within populations represent a powerful basis to develop novel therapies aiming to prolong cardiovascular and whole organism health.
再生医学是一种新的治疗方式，旨在通过促进生理完整性的重建来修复组织损伤。它代表了相对于传统疗法的进步，传统疗法虽能减少损伤，但会导致疾病慢性化。与年龄相关的自发修复能力下降，尤其是在像心脏这样增殖能力非常有限的器官中，会降低传统疗法的疗效。非编码RNA正成为心血管再生的关键表观遗传调节因子。抑制或替代微小RNA可能为心血管疾病提供修复解决方案。这篇综述文章的第一部分致力于阐述基于微小RNA研究而出现的新疗法。在第二部分中，我们探讨了从长寿遗传学中衍生出的新治疗概念。像超级百岁老人那样的长期存活表明其具有非凡的修复能力以及应对风险因素和疾病的能力。这些特征在其后代中也有体现，这表明再生表型是可遗传的。新证据表明，人类中负责延长健康寿命的遗传特征可以传递给心血管疾病动物模型，并改善其结果。遗传学研究还聚焦于加速衰老的决定因素以及相关的可药物作用靶点。评估适应的遗传基础并比较种群内对选择的成功和不成功遗传变化的进化遗传学，是开发旨在延长心血管和整个生物体健康的新疗法的有力基础。
