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Vascular endothelium in atherosclerosis

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Abstract

Their strategic location between blood and tissue and their constitutive properties allow endothelial cells (EC) to monitor the transport of plasma molecules, by employing bidirectional receptor-mediated and receptor-independent transcytosis and endocytosis, and to regulate vascular tone, cellular cholesterol and lipid homeostasis. These cells are also involved in signal transduction, immunity, inflammation and haemostasis. Cardiovascular risk factors, such as hyperlipaemia/dyslipidaemia trigger the molecular machinery of EC to respond to insults by modulation of their constitutive functions followed by dysfunction and ultimately by injury and apoptosis. The gradual activation of EC consists initially in the modulation of two constitutive functions: (1) permeability, i.e. increased transcytosis of lipoproteins, and (2) biosynthetic activity, i.e. enhanced synthesis of the basement membrane and extracellular matrix. The increased transcytosis and the reduced efflux of β-lipoproteins (βLp) lead to their retention within the endothelial hyperplasic basal lamina as modified lipoproteins (MLp) and to their subsequent alteration (oxidation, glycation, enzymatic modifications). MLp generate chemoattractant and inflammatory molecules, triggering EC dysfunction (appearance of new adhesion molecules, secretion of chemokines, cytokines), characterised by monocyte recruitment, adhesion, diapedesis and residence within the subendothelium. In time, EC in the athero-prone areas alter their net negative surface charge, losing their non-thrombogenic ability, become loaded with lipid droplets and turn into foam cells. Prolonged and/or repeated exposure to cardiovascular risk factors can ultimately exhaust the protective effect of the endogenous anti-inflammatory system within EC. As a consequence, EC may progress to senescence, lose their integrity and detach into the circulation.

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Acknowledgments

This review is a tribute to the memory of our eminent mentor, Professor Nicolae Simionescu, who initiated most of the projects reviewed here. The work of many colleagues who over the years have contributed to the presented data is gratefully acknowledged.

Sources of Funding

The work was supported by grants from NIH-USA, the European Community and the COST Action BM0602, the Romanian Academy, and the Romanian Ministry for Education and Research.

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

    Anca V. Sima, Camelia S. Stancu & Maya Simionescu

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  1. Anca V. Sima
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  2. Camelia S. Stancu
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  3. Maya Simionescu
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Correspondence to Anca V. Sima.

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Sima, A.V., Stancu, C.S. & Simionescu, M. Vascular endothelium in atherosclerosis. Cell Tissue Res 335, 191–203 (2009). https://doi.org/10.1007/s00441-008-0678-5

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