低密度脂蛋白受体(LDLR)基因家族包括LDLR,非常LDLR,和LDL受体相关蛋白(LRP),如LRP1,LRP1b(又名LRP-DIT),LRP2(又名megalin),LRP4、LRP5/6和LRP8(akaApoER2)。LDLR家族成员构成了一类密切相关的多功能,跨膜受体,具有不同的功能,从胚胎发育到癌症,脂质代谢,和心血管稳态。虽然LDLR家族成员已经在动脉粥样硬化的背景下在全身循环中进行了广泛的研究,它们在肺动脉高压(PAH)中的作用还未得到充分的研究和很大程度上未知.内皮功能障碍,单核细胞的组织浸润,肺动脉平滑肌细胞的增殖是PAH的标志,导致血管重塑,抹杀,肺血管阻力增加,心力衰竭,和死亡。LDLR家族成员通过控制许多在PAH中失调的途径与上述有害过程纠缠在一起;这些途径包括脂质代谢和氧化,还有血小板衍生生长因子,转化生长因子β1,Wnt,载脂蛋白E,骨形态发生蛋白,和过氧化物酶体增殖物激活受体γ。在本文中,我们讨论了PAH中LDLR家族成员的最新知识。我们还回顾了在PAH以外的生物学环境和疾病中发现的机制和药物,这些机制和药物可能与高血压肺血管系统以及PAH或其他慢性,进步,使人衰弱的心血管疾病。
The low-density lipoprotein receptor (LDLR) gene family includes LDLR, very LDLR, and LDL receptor-related proteins (LRPs) such as LRP1, LRP1b (aka LRP-DIT), LRP2 (aka megalin), LRP4, and LRP5/6, and LRP8 (aka ApoER2). LDLR family members constitute a class of closely related multifunctional, transmembrane receptors, with diverse functions, from embryonic development to cancer, lipid metabolism, and cardiovascular homeostasis. While LDLR family members have been studied extensively in the systemic circulation in the context of atherosclerosis, their roles in pulmonary arterial hypertension (PAH) are understudied and largely unknown. Endothelial dysfunction, tissue infiltration of monocytes, and proliferation of pulmonary artery smooth muscle cells are hallmarks of PAH, leading to vascular remodeling, obliteration, increased pulmonary vascular resistance, heart failure, and death. LDLR family members are entangled with the aforementioned detrimental processes by controlling many pathways that are dysregulated in PAH; these include lipid metabolism and oxidation, but also platelet-derived growth factor, transforming growth factor β1, Wnt, apolipoprotein E, bone morpohogenetic proteins, and peroxisome proliferator-activated receptor gamma. In this paper, we discuss the current knowledge on LDLR family members in PAH. We also review mechanisms and drugs discovered in biological contexts and diseases other than PAH that are likely very relevant in the hypertensive pulmonary vasculature and the future care of patients with PAH or other chronic, progressive, debilitating cardiovascular diseases.