Interplay of Low-Density Lipoprotein Receptors, LRPs, and Lipoproteins in Pulmonary Hypertension

Laurent Calvier, Joachim Herz, Georg Hansmann

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)164-180
Number of pages17
JournalJACC: Basic to Translational Science
Volume7
Issue number2
DOIs
StatePublished - Feb 2022

Keywords

  • Apoer2
  • BMP
  • BMPR2
  • LDL receptor related protein
  • LDLR
  • LRP
  • LRP1
  • LRP1B
  • LRP2
  • LRP4
  • LRP5
  • LRP6
  • LRP8
  • MEgf7
  • PAH
  • PDGF
  • PPARγ
  • PVD
  • RVHF
  • TGF-β1
  • VLDLR
  • Wnt
  • apolipoprotein E receptor 2
  • endothelial cell
  • gp330
  • low-density lipoprotein receptor
  • megalin
  • monocyte
  • multiple epidermal growth factor-like domains 7
  • pulmonary arterial hypertension
  • pulmonary vascular disease
  • right ventricle heart failure
  • smooth muscle cell
  • very low density lipoprotein receptor
  • β-catenin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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