Intermediate monocytes (IM) exhibit proinflammatory properties and contribute to atherosclerosis. Elevated lipoprotein(a) [Lp(a)] levels modulate monocyte behavior, while proprotein convertase subtili Show more
Intermediate monocytes (IM) exhibit proinflammatory properties and contribute to atherosclerosis. Elevated lipoprotein(a) [Lp(a)] levels modulate monocyte behavior, while proprotein convertase subtilisin/kexin type 9 (PCSK9) has been implicated in inflammatory pathways beyond lipid metabolism. The effects of PCSK9 inhibition on monocyte subset distribution in high-risk coronary artery disease patients remain unclear. To assess the effects of lipoprotein fractions and PCSK9 inhibitor (PCSK9i) therapy on monocyte subset distribution in patients with stable coronary artery disease and highly elevated Lp(a) levels. We followed 100 statin-treated patients in the stable phase after myocardial infarction with highly elevated Lp(a), randomized to PCSK9i or placebo for six months. Biochemical, genetic, and cellular analyses were performed at baseline and follow-up. At baseline, IM levels correlated with total cholesterol (ρ = -0.202, In high-risk patients, PCSK9 inhibition modulates monocyte-lipoprotein interactions without affecting the monocyte subset distribution. PCSK9 may promote vascular inflammation through CCL2 regulation, which appears more closely related to Lp(a) composition than its circulating concentration. NCT04613167; https://www.clinicaltrials.gov/study/NCT04613167, date of registration: 6th of October 2020. Show less
Atherosclerosis is an active interaction between lipoproteins and inflammatory cells. Monocytes and macrophages are the most important immune cells involved in the process of atherosclerosis. They int Show more
Atherosclerosis is an active interaction between lipoproteins and inflammatory cells. Monocytes and macrophages are the most important immune cells involved in the process of atherosclerosis. They interact with atherogenic lipoproteins, in particular low density lipoprotein (LDL) cholesterol and lipoprotein(a) (Lp(a)). The increased concentration of the LDL cholesterol and Lp(a) accelerates the polarization of monocytes and macrophages toward proinflammatory phenotype and the formation of the foam cells. These cells then release large quantities of inflammatory cytokines that stimulate the oxidation of atherogenic lipoproteins that are even more atherogenic and contribute to the formation of foam cells and the secretion of the pro-inflammatory cytokines, thus creating a vicious circle. Surface marker C-C chemokine receptor type 2, expressed on monocytes/macrophages, enables their adhesion and migration into the subendothelial layer. The rupture of the atherosclerotic plaque on one hand, and the ability of the oxidized LDL cholesterol and Lp(a) to trigger arterial thrombosis by different mechanisms on the other hand, result in acute cardiovascular event. Here, we summarize the role of the monocytes and macrophages in atherosclerosis and explore the influence of LDL cholesterol and Lp(a) on monocytes and macrophages during the entire process of atherosclerosis, from its initiation to progression. Show less