Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy.
Laboratory of Epigenetics, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy.
Int J Mol Sci. 2019 Jun 24;20(12):3079. doi: 10.3390/ijms20123079.
Cardiovascular diseases (CVDs) are the most serious health problem in the world, displaying high rates of morbidity and mortality. One of the main risk factors for CVDs is age. Indeed, several mechanisms are at play during aging, determining the functional decline of the cardiovascular system. Aging cells and tissues are characterized by diminished autophagy, causing the accumulation of damaged proteins and mitochondria, as well as by increased levels of oxidative stress, apoptosis, senescence and inflammation. These processes can induce a rapid deterioration of cellular quality-control systems. However, the molecular mechanisms of age-associated CVDs are only partially known, hampering the development of novel therapeutic strategies. Evidence has emerged indicating that noncoding RNAs (ncRNAs), such as long ncRNAs (lncRNAs) and micro RNAs (miRNAs), are implicated in most patho-physiological mechanisms. Specifically, lncRNAs can bind miRNAs and act as competing endogenous-RNAs (ceRNAs), therefore modulating the levels of the mRNAs targeted by the sponged miRNA. These complex lncRNA/miRNA/mRNA networks, by regulating autophagy, apoptosis, necrosis, senescence and inflammation, play a crucial role in the development of age-dependent CVDs. In this review, the emerging knowledge on lncRNA/miRNA/mRNA networks will be summarized and the way in which they influence age-related CVDs development will be discussed.
心血管疾病(CVDs)是全球最严重的健康问题,其发病率和死亡率都很高。CVDs 的一个主要危险因素是年龄。事实上,在衰老过程中有几种机制在起作用,决定了心血管系统的功能下降。衰老的细胞和组织的特征是自噬减少,导致损伤蛋白和线粒体的积累,以及氧化应激、细胞凋亡、衰老和炎症水平的增加。这些过程会导致细胞质量控制系统迅速恶化。然而,与年龄相关的 CVD 的分子机制仅部分已知,这阻碍了新的治疗策略的发展。有证据表明,非编码 RNA(ncRNAs),如长 ncRNAs(lncRNAs)和 microRNAs(miRNAs),与大多数病理生理机制有关。具体来说,lncRNA 可以结合 miRNA 并作为竞争性内源 RNA(ceRNA),从而调节被海绵 miRNA 靶向的 mRNA 的水平。这些复杂的 lncRNA/miRNA/mRNA 网络通过调节自噬、细胞凋亡、坏死、衰老和炎症,在年龄依赖性 CVD 的发展中起着至关重要的作用。在这篇综述中,将总结 lncRNA/miRNA/mRNA 网络的新发现知识,并讨论它们影响与年龄相关的 CVD 发展的方式。