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Review
. 2024 Dec 6:11:1470364.
doi: 10.3389/fcvm.2024.1470364. eCollection 2024.

Atherogenic circulating lipoproteins in ischemic stroke

Affiliations
Review

Atherogenic circulating lipoproteins in ischemic stroke

Sonia Benitez et al. Front Cardiovasc Med. .

Abstract

The fundamental role of qualitative alterations of lipoproteins in the early development of atherosclerosis has been widely demonstrated. Modified low-density lipoproteins (LDL), such as oxidized LDL (oxLDL), small dense LDL (sdLDL), and electronegative LDL [LDL(-)], are capable of triggering the atherogenic process, favoring the subendothelial accumulation of cholesterol and promoting inflammatory, proliferative, and apoptotic processes characteristic of atherosclerotic lesions. In contrast, high-density lipoprotein (HDL) prevents and/or reverses these atherogenic effects. However, LDL's atherogenic and HDL's anti-atherogenic actions may result altered in certain pathological conditions. The molecular mechanisms underlying the impaired effects of altered lipoproteins have been studied in numerous in vitro and in vivo studies, and have been extensively analyzed in coronary atherosclerosis, especially in the context of pathologies such as dyslipidemia, diabetes, obesity, and metabolic syndrome. However, the corresponding studies are scarcer in the field of ischemic stroke, despite carotid arteriosclerosis progression underlies at least 20% of ischemic strokes. The present review relates qualitative alterations of LDL and HDL with the development of carotid arteriosclerosis and the occurrence of ischemic stroke.

Keywords: HDL; carotid atherosclerosis; electronegative LDL; ischemic stroke; oxidized LDL; small dense LDL.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Role of LDL and HDL in atherogenesis. LDL entry to the microenvironment of the subendothelial space favors chemical modifications resulting from oxidative stress and the actions of lipolytic and proteolytic enzymes. These modifications favor LDL aggregation and increased binding to proteoglycans, facilitating its subendothelial retention. Retained modified LDL particles induce endothelial dysfunction, the recruitment of leukocytes with enhanced inflammatory response, the differentiation of monocytes into macrophages, the emergence of apoptotic processes, and the formation of lipid-loaded foam cells. Together, all of these events lead to the development of the atherosclerotic plaque. The atherogenic effects of LDL are indicated with blue arrows. In contrast, HDL particles that enter in the arterial wall can prevent LDL oxidation and aggregation, and display anti-inflammatory, antiproliferative and antiapoptotic properties (brown arrows). In addition, HDL induces the efflux of cholesterol from lipid-loaded foam cells and returning the excess of cholesterol to blood circulation for its metabolization in the liver.
Figure 2
Figure 2
LDL modification. Besides the modification of LDL in the arterial wall, LDL particles can also suffer different alterations in blood, leading to modified LDL particles. Alterations in VLDL-IDL-LDL catabolic cascade or in the lipid transfer processes among lipoproteins can favor the formation of sdLDL or LDL(-). Other processes, such as overload of non-esterified fatty acids or oxidative phenomena occurring in blood can also lead to the formation of LDL(-) or oxLDL. All these modified LDL particles will contribute to the development of atherosclerosis. In turn, the rupture of the atherosclerotic plaque after an ischemic event can release its content of modified lipoproteins, thereby contributing to the plasma pool of LDL(-) and oxLDL. For its part, HDL plays an antiatherogenic role, preventing the formation of modified LDL, through its antioxidant capacity or the ability to capture non-esterified fatty acids.

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