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Dual role of lipoproteins in endothelial cell dysfunction in atherosclerosis

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Abstract

The endothelium is a key constituent of the vascular wall, being actively involved in maintaining the structural integrity and proper functioning of blood vessels. Hyperlipidemia, diabetes, hypertension, smoking and aging are important risk factors for the dysfunction of endothelial cells (EC). Circulating lipoproteins (Lp) synthesized and secreted from the intestine or liver have an important role in supplying peripheral tissues with fatty acids from triglyceride rich lipoproteins (TGRLp) for energy production or storage, and cholesterol from low density lipoproteins (LDL) or high density lipoproteins (HDL) for the synthesis of cellular membranes and steroid hormones. Under pathological conditions, Lp may suffer alterations in concentration and composition and become aggressors for EC. Modified LDL, remnant Lp, TGRLp lipolysis products, dysfunctional HDL are involved in the changes induced in EC morphology (reduced glycocalyx, overdeveloped endoplasmic reticulum, Golgi apparatus and basement membrane), loose intercellular junctions, increased oxidative and inflammatory stress, nitric oxide/redox imbalance, excess Lp transport and storage, as well as loss of anti-thrombotic properties, all of these being characteristics of endothelial dysfunction. Normal HDL are able to counteract the harmful effects of atherogenic Lp in EC but under persistent pathological conditions they lose the protective properties and become pro-atherogenic. This review summarises recent advances in understanding the role of Lp in the induction of endothelial dysfunction and the initiation and progression of atherosclerotic lesions. Its main focus is the antagonistic role of atherogenic Lp (LDL, VLDL, dysfunctional HDL) versus anti-atherogenic Lp (HDL), also pointing out the potential targets for arresting or reversing this process.

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Acknowledgement

The authors wish to express their gratitude to Prof. Maya Simionescu for most valuable scientific discussions and constant support. We thank all the researchers who helped us understand the mechanisms linking dysfunctional lipoproteins to dysfunctional endothelium. This review was funded from grants obtained from the Romanian Ministry of Education and Research and the Romanian Academy.

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  1. Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P.Hasdeu Street, 050568, Bucharest, Romania

    Camelia S. Stancu, Laura Toma & Anca V. Sima

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  1. Camelia S. Stancu
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  2. Laura Toma
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  3. Anca V. Sima
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Correspondence to Anca V. Sima.

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Stancu, C.S., Toma, L. & Sima, A.V. Dual role of lipoproteins in endothelial cell dysfunction in atherosclerosis. Cell Tissue Res 349, 433–446 (2012). https://doi.org/10.1007/s00441-012-1437-1

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