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Defining Characteristics of Angiogenesis Regulation in Advanced Human Carotid Plaques

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Abstract

Increased neovascularization of the atherosclerotic plaque promotes plaque vulnerability, atherosclerosis progression, and increased risk of complications, including myocardial infarction and ischemic stroke. The aim of our study was a comprehensive assessment of the expression of multidirectional regulatory factors of angiogenesis in a carotid atherosclerotic plaque. The study included 33 patients with atherosclerotic carotid stenosis exceeding 60%, who were exposed to carotid endarterectomy followed by pathomorphological examination of removed atherosclerotic plaques throughout their length. The structure of plaques, the number of microvessels per 1 cm2 of the plaque, as well as the expression of vascular endothelial growth factors (VEGFA, VEGFB, VEGFC, and VEGFD) and their receptors (VEGFR1, VEGFR2, VEGFR3), FGF2, PDGF-B, and TSP-1) were assessed using histological and immunohistochemical methods followed by a correlation analysis. According to histological examination, 13 plaques were referred to atheromatous (type Va), 12 to complicated, with either fibrous cap ulceration or massive intraplaque haemorrhage (type VI), 6 to calcified (type Vb), and 2 to fibrous (type Vc). Neovessels were found in all plaques (267.5 vessels/1 cm2 [140.9; 534.8]). Most of the neovessels had a highly permeable phenotype with such features as the compromised endothelial integrity, lack of the pericyte layer, and perivascular hemorrhage. VEGFD was overexpressed, significantly prevailing over the other assessed factors (p < 0.001). The pronounced expression of VEGFA, VEGFR2, VEGFR3, FGF2 and PDGF-B was also found in plaques. Immunoreactivity to VEGFB, VEGFC and TSP-1 was the least, with VEGFR1 detected in trace amounts. The number of plaque microvessels significantly correlated with the expression of VEGFA, VEGFD, FGF2, PDGF-B and VEGFR2 (p < 0.01). Other structural components of the plaque did not correlate with the level of angiogenic factors therein. Thus, we demonstrated a pronounced proangiogenic expression profile of various angiogenic factors in association with a failure of the neovasculature stabilization mechanism in advanced human carotid atherosclerotic plaques.

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Funding

This study was implemented within the state assignment to the Research Center of Neurology for basic scientific research.

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Authors and Affiliations

  1. Research Center of Neurology, Moscow, Russia

    A. N. Evdokimenko, K. N. Kulichenkova, T. S. Gulevskaya & M. M. Tanashyan

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  1. A. N. Evdokimenko
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  2. K. N. Kulichenkova
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  3. T. S. Gulevskaya
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Contributions

A.N.E.—conceptualization, experimental design, data collection and processing, writing a manuscript; K.N.K.—data collection and processing, writing a manuscript; T.S.G.—conceptualization and experimental design, writing and editing a manuscript; M.M.T.—conceptualization and experimental design, writing and editing a manuscript.

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Correspondence to A. N. Evdokimenko.

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The authors declare that they have neither evident nor potential conflict of interest associated with the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 5, pp. 649–666https://doi.org/10.31857/S0869813922050041.

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Evdokimenko, A.N., Kulichenkova, K.N., Gulevskaya, T.S. et al. Defining Characteristics of Angiogenesis Regulation in Advanced Human Carotid Plaques. J Evol Biochem Phys 58, 825–840 (2022). https://doi.org/10.1134/S0022093022030164

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