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

© 2022 The Authors..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:7

Enthalten in:

JACC. Basic to translational science - 7(2022), 2 vom: 04. Feb., Seite 164-180

Sprache:

Englisch

Beteiligte Personen:

Calvier, Laurent [VerfasserIn]
Herz, Joachim [VerfasserIn]
Hansmann, Georg [VerfasserIn]

Links:

Volltext

Themen:

β-catenin
ApoE, apolipoprotein E
Apoer2
Apolipoprotein E receptor 2
BMP
BMPR, bone morphogenetic protein receptor
BMPR2
COPD, chronic obstructive pulmonary disease
CTGF, connective tissue growth factor
Endothelial cell
Gp330
HDL, high-density lipoprotein
Journal Article
KO, knockout
LDL, low-density lipoprotein
LDL receptor related protein
LDLR
LDLR, low-density lipoprotein receptor
LRP
LRP, low-density lipoprotein receptor–related protein
LRP1
LRP1B
LRP2
LRP4
LRP5
LRP6
LRP8
Low-density lipoprotein receptor
MEgf7
MRNA, messenger RNA
Megalin
Mesd, mesoderm development
Monocyte
Multiple epidermal growth factor-like domains 7
PAH
PAH, pulmonary arterial hypertension
PASMC, pulmonary artery smooth muscle cell
PDGF
PDGFR-β, platelet-derived growth factor receptor-β
PH, pulmonary hypertension
PPARγ
PPARγ, peroxisome proliferator-activated receptor gamma
PVD
Pulmonary arterial hypertension
Pulmonary vascular disease
RV, right ventricle/ventricular
RVHF
RVSP, right ventricular systolic pressure
Review
Right ventricle heart failure
Smooth muscle cell
TGF-β1
TGF-β1, transforming growth factor β1
TGFBR, transforming growth factor β1 receptor
TNF, tumor necrosis factor receptor
VLDLR
VLDLR, very low density lipoprotein receptor
VSMC, vascular smooth muscle cell
Very low density lipoprotein receptor
Wnt

Anmerkungen:

Date Revised 18.05.2022

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.1016/j.jacbts.2021.09.011

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM337880484