Lipoprotein (a)-Related Inflammatory Imbalance: A Novel Horizon for the Development of Atherosclerosis

Overview

Journal Curr Atheroscler Rep

Publisher Springer

Specialty Cardiology & Vascular Diseases

Date 2024 Jun 15

PMID 38878139

Authors

Ting Qin

Tian-Yi Ma

Kang Huang

Shi-Juan Lu

Jiang-Hua Zhong

Jian-Jun Li

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: The primary objective of this review is to explore the pathophysiological roles and clinical implications of lipoprotein(a) [Lp(a)] in the context of atherosclerotic cardiovascular disease (ASCVD). We seek to understand how Lp(a) contributes to inflammation and arteriosclerosis, aiming to provide new insights into the mechanisms of ASCVD progression.

Recent Findings: Recent research highlights Lp(a) as an independent risk factor for ASCVD. Studies show that Lp(a) not only promotes the inflammatory processes but also interacts with various cellular components, leading to endothelial dysfunction and smooth muscle cell proliferation. The dual role of Lp(a) in both instigating and, under certain conditions, mitigating inflammation is particularly noteworthy. This review finds that Lp(a) plays a complex role in the development of ASCVD through its involvement in inflammatory pathways. The interplay between Lp(a) levels and inflammatory responses highlights its potential as a target for therapeutic intervention. These insights could pave the way for novel approaches in managing and preventing ASCVD, urging further investigation into Lp(a) as a therapeutic target.

References

Ridker P . From C-Reactive Protein to Interleukin-6 to Interleukin-1: Moving Upstream To Identify Novel Targets for Atheroprotection. Circ Res. 2016; 118(1):145-56. PMC: 4793711. DOI: 10.1161/CIRCRESAHA.115.306656. View

Riches K, Porter K . Lipoprotein(a): Cellular Effects and Molecular Mechanisms. Cholesterol. 2012; 2012:923289. PMC: 3443569. DOI: 10.1155/2012/923289. View

Pokrovsky S, Afanasieva O, Safarova M, Balakhonova T, Matchin Y, Adamova I . Specific Lp(a) apheresis: A tool to prove lipoprotein(a) atherogenicity. Atheroscler Suppl. 2017; 30:166-173. DOI: 10.1016/j.atherosclerosissup.2017.05.004. View

Allen S, Khan S, Tam S, Koschinsky M, Taylor P, Yacoub M . Expression of adhesion molecules by lp(a): a potential novel mechanism for its atherogenicity. FASEB J. 1998; 12(15):1765-76. DOI: 10.1096/fasebj.12.15.1765. View

Guvener M, Ucar I, Ozkan M, Dogan O, Serter F, Pasaoglu I . Effect of cardiopulmonary bypass on plasma levels of lipoprotein (a) in hypercholesterolemic patients. Jpn Heart J. 2002; 42(5):563-74. DOI: 10.1536/jhj.42.563. View

Koutsogianni A, Liberopoulos E, Tellis K, Tselepis A . Oxidized phospholipids and lipoprotein(a): An update. Eur J Clin Invest. 2021; 52(4):e13710. DOI: 10.1111/eci.13710. View

Pellegrino M, Furmaniak-Kazmierczak E, LeBlanc J, Cho T, Cao K, Marcovina S . The apolipoprotein(a) component of lipoprotein(a) stimulates actin stress fiber formation and loss of cell-cell contact in cultured endothelial cells. J Biol Chem. 2003; 279(8):6526-33. DOI: 10.1074/jbc.M309705200. View

Ray K, Wright R, Kallend D, Koenig W, Leiter L, Raal F . Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020; 382(16):1507-1519. DOI: 10.1056/NEJMoa1912387. View

Lau F, Giugliano R . Lipoprotein(a) and its Significance in Cardiovascular Disease: A Review. JAMA Cardiol. 2022; 7(7):760-769. DOI: 10.1001/jamacardio.2022.0987. View

10.

Seok J, Hong E, Yang G, Lee H, Kim S, Liu K . Oxidized Phospholipids in Tumor Microenvironment Stimulate Tumor Metastasis via Regulation of Autophagy. Cells. 2021; 10(3). PMC: 8001732. DOI: 10.3390/cells10030558. View

11.

van der Valk F, Bekkering S, Kroon J, Yeang C, Van den Bossche J, van Buul J . Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans. Circulation. 2016; 134(8):611-24. PMC: 4995139. DOI: 10.1161/CIRCULATIONAHA.116.020838. View

12.

Ridker P . How Common Is Residual Inflammatory Risk?. Circ Res. 2017; 120(4):617-619. DOI: 10.1161/CIRCRESAHA.116.310527. View

13.

Briot A, Civelek M, Seki A, Hoi K, Mack J, Lee S . Endothelial NOTCH1 is suppressed by circulating lipids and antagonizes inflammation during atherosclerosis. J Exp Med. 2015; 212(12):2147-63. PMC: 4647265. DOI: 10.1084/jem.20150603. View

14.

Kamstrup P, Tybjaerg-Hansen A, Nordestgaard B . Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis. Arterioscler Thromb Vasc Biol. 2012; 32(7):1732-41. DOI: 10.1161/ATVBAHA.112.248765. View

15.

Sabbah N, Jaisson S, Garnotel R, Angles-Cano E, Gillery P . Small size apolipoprotein(a) isoforms enhance inflammatory and proteolytic potential of collagen-primed monocytes. Lipids Health Dis. 2019; 18(1):166. PMC: 6717332. DOI: 10.1186/s12944-019-1106-4. View

16.

Zhao S, Xu D . Oxidized lipoprotein(a) increases the expression of platelet-derived growth factor-B in human umbilical vein endothelial cells. Clin Chim Acta. 2000; 296(1-2):121-33. DOI: 10.1016/s0009-8981(00)00214-x. View

17.

Santos R, Raal F, Catapano A, Witztum J, Steinhagen-Thiessen E, Tsimikas S . Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: results of 4 phase III trials. Arterioscler Thromb Vasc Biol. 2015; 35(3):689-99. PMC: 4344404. DOI: 10.1161/ATVBAHA.114.304549. View

18.

Kamstrup P, Benn M, Tybjaerg-Hansen A, Nordestgaard B . Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation. 2007; 117(2):176-84. DOI: 10.1161/CIRCULATIONAHA.107.715698. View

19.

Cybulska B, Klosiewicz-Latoszek L, Penson P, Banach M . What do we know about the role of lipoprotein(a) in atherogenesis 57 years after its discovery?. Prog Cardiovasc Dis. 2020; 63(3):219-227. DOI: 10.1016/j.pcad.2020.04.004. View

20.

Leibundgut G, Scipione C, Yin H, Schneider M, Boffa M, Green S . Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a). J Lipid Res. 2013; 54(10):2815-30. PMC: 3770094. DOI: 10.1194/jlr.M040733. View