Involvement of the excretory/secretory and surface-associated antigens of Dirofilaria immitis adult worms in the angiogenic response in an in-vitro endothelial cell model.

Autor: Machado CDC; Zoonotic Diseases and One Health group, IBSAL-CIETUS (Biomedical Research Institute of Salamanca-Research Centre for Tropical Diseases University of Salamanca), Faculty of Pharmacy, University of Salamanca, 37007, Salamanca, Spain., Alarcón-Torrecillas C; Department of Physiology and Pharmacology, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain., Pericacho M; Department of Physiology and Pharmacology, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain., Rodríguez-Escolar I; Zoonotic Diseases and One Health group, IBSAL-CIETUS (Biomedical Research Institute of Salamanca-Research Centre for Tropical Diseases University of Salamanca), Faculty of Pharmacy, University of Salamanca, 37007, Salamanca, Spain., Carretón E; Faculty of Veterinary Medicine, Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Arucas, 35413, Las Palmas, Spain., Montoya-Alonso JA; Faculty of Veterinary Medicine, Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Arucas, 35413, Las Palmas, Spain., Morchón R; Zoonotic Diseases and One Health group, IBSAL-CIETUS (Biomedical Research Institute of Salamanca-Research Centre for Tropical Diseases University of Salamanca), Faculty of Pharmacy, University of Salamanca, 37007, Salamanca, Spain. Electronic address: rmorgar@usal.es.
Jazyk: angličtina
Zdroj: Veterinary parasitology [Vet Parasitol] 2023 Jun; Vol. 318, pp. 109939. Date of Electronic Publication: 2023 Apr 27.
DOI: 10.1016/j.vetpar.2023.109939
Abstrakt: Angiogenesis is a process by which new vessels are formed from pre-existing ones when the physiological conditions of the vascular endothelium are altered. Heartworm disease, caused by Dirofilaria immitis, causes changes in the vascular endothelium of the pulmonary arteries due to obstruction, friction, and hypoxia. The aim of this study was to analyze whether the excretory/secretory and surface-associated antigens of adult worms interact and modulates the angiogenic mechanism, viable cell number and cell migration, as well as the formation of pseudo-capillaries. Cultures of human vascular endothelial cells (HUVECs) stimulated with excretory/secretory antigens (DiES), surface-associated antigens (Cut) from D. immitis adult worms, VEFG-A (Vascular Endothelial Growth Factor A), as well as DiES+VEFG-A and Cut+VEFG-A were used. The production of VEFG-A and other proangiogenic [soluble VEFGR-2 (sVEFGR-2), membrane Endoglin (mEndoglin)] and antiangiogenic [VEFGR-1/soluble Flt (sFlt), soluble Endoglin (sEndoglin)] molecules was assessed using commercial ELISA kits. Cell viability was analyzed by live cell count and cytotoxicity assays by a commercial kit. In addition, viable cell number by MTT-based assay, cell migration by wound-healing assay carrying out scratched wounds, and the capacity of pseudo-capillary formation to analyze cell connections and cell groups in Matrigel cell cultures, were evaluated. In all cases, non‑stimulated cultures were used as controls. DiES+VEFG-A and Cut+VEFG-A significantly increased the production of VEFG-A and sVEFGR-2, and only Cut+VEFG-A significantly increased the production of VEFGR-1/sFlt compared to other groups and non-stimulated cultures. Moreover, only DiES+VEFG-A produced a significant increase in viable cell number and significant decrease cell migration, as well as in the organization and number of cell connections. Excretory/secretory and surface-associated antigens of adult D. immitis activated the angiogenic mechanism by mainly stimulating the synthesis of proangiogenic factors, and only excretory/secretory antigens increased viable cell number, activated cell migration and the formation of pseudo-capillaries. These processes could lead to vascular endothelial remodeling of the infected host and favor the long-term survival of the parasite.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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