Abstract
Recent studies showed that pathologies associated with aging, such as cardiovascular disease and osteoarthritis (OA), can have several common molecular and cellular pathophysiological mechanisms. The conditions and extent of influence of arterial hypertension (AH) and hyperlipidemia (HL) on joint tissues remain unclear. This work investigates the role of vascular endothelial growth factor (VEGF-A), adiponectin (Adipo), and matrix metalloproteinase-9 (MMP-9) in the remodeling of articular cartilage (AC) and subchondral bone (SCB) in experimental AH and HL. The experimental study was carried out on 18 sexually mature outbred male guinea pigs, which were divided into three groups of six individuals in each: the first group included animals with modeled AH, the second included those with modeled HL, and the third group consisted of intact animals (control). All animals were withdrawn on the 60th day of the experiment, and tissues from the knee joints of the hind legs were sampled. The expression of VEGF-A, Adipo, and MMP-9 in the joint tissues was determined. The results of the study revealed that, under the influence of AH and HL, AC and SCB experience cellular stress caused by endothelium-dependent dysmetabolism. Our study shows that extravasal expression of VEGF-A is observed under experimental AH conditions and is most pronounced with SCB. In addition, moderate expression of Adipo and MMP-9 in SCB is noted. Overexpression of VEGF-A in AC is noted for systemic HL under experimental conditions. The obtained data indicate that SCB and AC are target organs of cardiovascular factors. The effects of AH and HL seem to trigger processes of nonadaptive osteogenesis and ectopic angioproliferation, which contribute to the formation of a pathogenetic model of OA.
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ACKNOWLEDGMENTS
The authors are grateful to the Head of the Research Laboratory of the Pacific State Medical University of the Ministry of Health of Russia Dr. Biol. Sciences Natal’ya Gennad’evna Plekhova for help in organizing morphological studies.
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This study was carried out with the financial support of a research grant from the Pacific State Medical University of the Ministry of Health of Russia.
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Statement on animal welfare. The study was carried out in accordance with the provisions of the Declaration of Helsinki and the recommendations of the European Community Directive (86/609 GS). The design and protocol of the experimental study was approved by the interdisciplinary ethics committee of the Pacific State Medical University of the Ministry of Health of Russia.
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Kabalyk, M.A., Nevzorova, V.A. Molecular and Cellular Mechanisms of Osteoarthritis in Experimental Arterial Hypertension and Hyperlipidemia. Adv Gerontol 11, 145–151 (2021). https://doi.org/10.1134/S2079057021020065
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DOI: https://doi.org/10.1134/S2079057021020065