Cardiovascular diseases (CVDs) are the first cause of death in the World. Mediator (MED) is an evolutionarily conserved protein complex, which mediates distinct protein-protein interactions. Pathogenic events in MED subunit have been associated with human diseases. Novel increasing evidence showed that missense mutations in MED13L gene are associated with transposition of great arteries while MED12, MED13, MED15, and MED30, have been correlated with heart development. Moreover, MED23 and MED25 have been associated with heart malformations in humans. Relevantly, MED1, MED13, MED14, MED15, MED23, MED25, and CDK8, were found modify glucose and/or lipid metabolism. Indeed, MED1, MED15, MED25, and CDK8 interact in the PPAR- and SREBP-mediated signaling pathways. MED1, MED14 and MED23 are involved in adipocyte differentiation, whereas MED23 mediates smooth muscle cell differentiation. MED12, MED19, MED23, and MED30 regulate endothelial differentiation by alternative splicing mechanism. Thus, MEDs have a central role in early pathogenic events involved in CVDs representing novel targets for clinical prevention and therapeutic approaches.

中文翻译：

---

越来越多的证据表明，介体（MED）复合物在心血管疾病的发展中具有致病作用。

心血管疾病（CVD）是世界上第一大死亡原因。介体（MED）是一种进化保守的蛋白质复合物，可介导不同的蛋白质-蛋白质相互作用。MED亚基的致病性事件与人类疾病有关。越来越多的新证据表明，MED13L基因的错义突变与大动脉的移位有关，而MED12，MED13，MED15和MED30与心脏发育相关。此外，MED23和MED25与人类心脏畸形有关。相关地，发现MED1，MED13，MED14，MED15，MED23，MED25和CDK8改变了葡萄糖和/或脂质代谢。实际上，MED1，MED15，MED25和CDK8在PPAR和SREBP介导的信号通路中相互作用。MED1，MED14和MED23参与脂肪细胞的分化，而MED23介导平滑肌细胞分化。MED12，MED19，MED23和MED30通过其他剪接机制调节内皮细胞分化。因此，MED在涉及CVD的早期致病事件中起着中心作用，代表了临床预防和治疗方法的新靶标。