Paredes Ana, Santos-Clemente Rocio, Ricote Mercedes
Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
Int J Mol Sci. 2021 Jul 21;22(15):7775. doi: 10.3390/ijms22157775.
The heart is the first organ to acquire its physiological function during development, enabling it to supply the organism with oxygen and nutrients. Given this early commitment, cardiomyocytes were traditionally considered transcriptionally stable cells fully committed to contractile function. However, growing evidence suggests that the maintenance of cardiac function in health and disease depends on transcriptional and epigenetic regulation. Several studies have revealed that the complex transcriptional alterations underlying cardiovascular disease (CVD) manifestations such as myocardial infarction and hypertrophy is mediated by cardiac retinoid X receptors (RXR) and their partners. RXRs are members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors and drive essential biological processes such as ion handling, mitochondrial biogenesis, and glucose and lipid metabolism. RXRs are thus attractive molecular targets for the development of effective pharmacological strategies for CVD treatment and prevention. In this review, we summarize current knowledge of RXR partnership biology in cardiac homeostasis and disease, providing an up-to-date view of the molecular mechanisms and cellular pathways that sustain cardiomyocyte physiology.
心脏是发育过程中首个获得其生理功能的器官，使其能够为机体提供氧气和营养物质。鉴于这种早期的功能设定，心肌细胞传统上被认为是完全致力于收缩功能的转录稳定细胞。然而，越来越多的证据表明，心脏功能在健康和疾病状态下的维持取决于转录和表观遗传调控。多项研究表明，心血管疾病（CVD）表现（如心肌梗死和肥大）背后复杂的转录改变是由心脏视黄酸X受体（RXR）及其伴侣介导的。RXR是配体激活转录因子核受体（NR）超家族的成员，驱动离子处理、线粒体生物发生以及葡萄糖和脂质代谢等重要生物学过程。因此，RXR是开发有效治疗和预防CVD药理学策略的有吸引力的分子靶点。在本综述中，我们总结了RXR伴侣生物学在心脏稳态和疾病方面的当前知识，提供了维持心肌细胞生理学的分子机制和细胞途径的最新观点。
