Interplay of Low-Density Lipoprotein Receptors, LRPs, and Lipoproteins in Pulmonary Hypertension.
Interplay of Low-Density Lipoprotein Receptors, LRPs, and Lipoproteins in Pulmonary Hypertension.
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DOI：
10.1016/j.jacbts.2021.09.011
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Hansmann G
中科院分区：
文献类型：
--
作者：
Calvier L;Herz J;Hansmann G
LDLR调节PAH患者肺和血液中氧化LDL水平升高。维持血管稳态的LRP1在PAH患者中减少。LRP5/6调节Wnt信号在ph中上调。LRP8（又名ApoER2）配体ApoE保护PAH。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（又名ApoER2）。LDLR家族成员构成了一类密切相关的多功能跨膜受体，具有多种功能，从胚胎发育到癌症、脂质代谢和心血管稳态。虽然LDLR家族成员在动脉粥样硬化背景下的体循环中被广泛研究，但它们在肺动脉高压（PAH）中的作用尚未得到充分研究，而且在很大程度上是未知的。内皮功能障碍、组织单核细胞浸润和肺动脉平滑肌细胞增生是PAH的特征，可导致血管重构、闭塞、肺血管阻力增加、心力衰竭和死亡。LDLR家族成员通过控制多环芳烃中失调的许多途径与上述有害过程纠缠在一起；这些包括脂质代谢和氧化，还有血小板衍生的生长因子、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。本文就LDLR家族成员在PAH中的研究进展进行综述。我们还回顾了在生物学背景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和PAH患者或其他慢性，进行性，衰弱性心血管疾病的未来护理非常相关。
LDLR regulates oxidized LDL level, which is increased in lung and blood from PAH patients. LRP1 preserving vascular homeostasis is decreased in PAH patients. LRP5/6 regulating Wnt signaling is upregulated in PH. The LRP8 (aka ApoER2) ligand ApoE protects from PAH. 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.
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影响因子：
3.7
作者：
Boucher, Philippe;Li, Wei-Ping;Matz, Rachel L.;Takayama, Yoshiharu;Auwerx, Johan;Anderson, Richard G. W.;Herz, Joachim
通讯作者：
Herz, Joachim
影响因子：
3.6
作者：
Alapati, Deepthi;Rong, Min;Wu, Shu
通讯作者：
Wu, Shu
影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
DOI：
10.1161/atvbaha.121.316000
发表时间：
2021-04
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Calvier L;Xian X;Lee RG;Sacharidou A;Mineo C;Shaul PW;Kounnas MZ;Tsai S;Herz J
通讯作者：
Herz J
影响因子：
5.6
作者：
Actis Dato V;Chiabrando GA
通讯作者：
Chiabrando GA