ARYA Atherosclerosis Journal

The effect of ox-LDL and platelets on macrophages, M2 macrophage polarization, and foam cell formation

Document Type : Original Article(s)

Authors

Fatemeh Barati 1
Davood Bashash 1
Mohamad Hosein Mohamadi 2
Mahdieh Mehrpori 3
Mohsen Hamidpour 2

1 Department of Hematology and Blood Banking, School of Allied Medical Sciences Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 HSC Research Center-Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical sciences, Tehran, Iran

3 Department of Laboratory Sciences, School of Allied Medical Sciences Alborz University of Medical Sciences, Karaj, Iran

https://doi.org/10.48305/arya.2022.11777.2422
Abstract
Background: The accumulation of oxidized LDL (ox-LDL) in macrophages in association with platelet activity leads to the formation of foam cells, which play a key role in the pathophysiology of atherosclerosis and coronary artery diseases (CAD). Here, in this study, we aimed to investigate the simultaneous effect of ox-LDL and platelets on foam cell formation, as well as modification in cell markers. 
Methods: First, the U937, a human monocytic cell line,  was cultured in RPMI-1640. Then, isolated platelets were co-cultured with the U937 and exposed to ox-LDL (80 µg/ml) to evaluate the impact of ox-LDL on foam cell formation using Oil red O (ORO) staining. Also, the expression of foam cells’ surface markers and CD36, ABCA1, SR-B1, ACAT1, and LXRα genes, which are involved in macrophage metabolism and ox-LDL uptake, was measured by flow cytometry and real-time PCR, respectively. 
Results: Our findings suggest that platelets promoted foam cell formation (ORO-positive cells), accompanied by a higher level of CD163+ M2 macrophages. Furthermore, the expression of CD36, ABCA1, SR-B1, ACAT1, and LXRα genes, which are implicated in cholesterol accumulation in macrophages, was significantly upregulated in the ox-LDL+ platelets group compared to the control (P < 0.05). Moreover, the up-regulation of CD36, ABCA1, and SR-B1 genes in the ox-LDL+ platelets group was more accentuated compared to the ox-LDL group (P < 0.05).
Conclusions: Owing to the positive effector role of platelets in the formation of foam cells and CD163+ cells, it could be assumed that platelets play a dual role in the development of these cells.

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Keywords

ox-LDL
Platelets
Macrophages
Foam cells
Atherosclerosis
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ARYA Atherosclerosis Journal
Volume 19, Issue 1
January 2023
Pages 25-33

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