TY - JOUR
T1 - Lipoprotein(a)
T2 - An underestimated inflammatory mastermind
AU - Dzobo, Kim E.
AU - Kraaijenhof, Jordan M.
AU - Stroes, Erik S. G.
AU - Nurmohamed, Nick S.
AU - Kroon, Jeffrey
N1 - Funding Information: This work was supported by the Netherlands Organization for Scientific Research . JK received a VENI grant from ZonMW ( 91619098 ) and was supported by the Dutch Heart Foundation (Senior Scientist Dekker grant (03-004-2021-T045)). Funding Information: NSN is co-founder of Lipid Tools. JK received a preclinical research grant from Oxitope Pharma B.V. ES has received lecturing ad-board fees, paid to institution, by Amgen, Sanofi, Novartis, Novo-Nordisk, Esperion and Ionis/Akcea. Publisher Copyright: © 2022 Elsevier B.V.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Lipoprotein(a) [Lp(a)] has been established as an independent and causal risk factor for cardiovascular disease. Individuals with elevated levels of Lp(a) (>125 nmol/L; >50 mg/dl) display increased arterial wall inflammation characterized by activation of the endothelium by Lp(a)-carried oxidized phospholipids and recruitment of circulating monocytes. This results in increased secretion of chemoattractants and cytokines, upregulation of adhesion molecules and increased migration of leukocytes through the vessel wall. In addition, Lp(a) is also pivotal in the initiation phase of aortic valve stenosis. The oxidized phospholipids associated, in part, with the apolipoprotein(a) [apo(a)] moiety of Lp(a) stimulate the aortic valve residential cell, the valve interstitial cells (VICs), to either induce osteoblastic differentiation or apoptosis, thereby initiating the process of aortic valve calcification. Lastly, Lp(a) has been linked to systemic inflammation, including the acute phase response. Specifically, the cytokine interleukin 6 (IL-6) has a unique relationship with Lp(a), since the LPA gene contains IL-6 response elements. In this review, we will discuss the pathways and cell types affected by Lp(a) in the context of atherosclerosis, aortic valve stenosis and the acute phase response, highlighting the role of Lp(a) as an inflammatory mastermind.
AB - Lipoprotein(a) [Lp(a)] has been established as an independent and causal risk factor for cardiovascular disease. Individuals with elevated levels of Lp(a) (>125 nmol/L; >50 mg/dl) display increased arterial wall inflammation characterized by activation of the endothelium by Lp(a)-carried oxidized phospholipids and recruitment of circulating monocytes. This results in increased secretion of chemoattractants and cytokines, upregulation of adhesion molecules and increased migration of leukocytes through the vessel wall. In addition, Lp(a) is also pivotal in the initiation phase of aortic valve stenosis. The oxidized phospholipids associated, in part, with the apolipoprotein(a) [apo(a)] moiety of Lp(a) stimulate the aortic valve residential cell, the valve interstitial cells (VICs), to either induce osteoblastic differentiation or apoptosis, thereby initiating the process of aortic valve calcification. Lastly, Lp(a) has been linked to systemic inflammation, including the acute phase response. Specifically, the cytokine interleukin 6 (IL-6) has a unique relationship with Lp(a), since the LPA gene contains IL-6 response elements. In this review, we will discuss the pathways and cell types affected by Lp(a) in the context of atherosclerosis, aortic valve stenosis and the acute phase response, highlighting the role of Lp(a) as an inflammatory mastermind.
KW - Acute phase
KW - Arterial wall inflammation
KW - Lipoprotein(a)
UR - http://www.scopus.com/inward/record.url?scp=85130399720&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.atherosclerosis.2022.04.004
DO - https://doi.org/10.1016/j.atherosclerosis.2022.04.004
M3 - Review article
C2 - 35606070
SN - 0021-9150
VL - 349
SP - 101
EP - 109
JO - Atherosclerosis
JF - Atherosclerosis
ER -