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Angiogenesis as a Survival Mechanism in Heartworm Disease: The Role of Fructose-Bisphosphate Aldolase and Actin from Dirofilaria immitis in an In Vitro Endothelial Model
by
, , , , and
Manuel Collado-Cuadrado
1
,
Claudia Alarcón-Torrecillas
2,
Alfonso Balmori-de la Puente
1,
Iván Rodríguez-Escolar
1,
Elena Infante González-Mohino
1,
Miguel Pericacho
2 and
Rodrigo Morchón
1,*
1
Zoonotic Diseases and One Health Group, Faculty of Pharmacy, Biomedical Research Institute of Salamanca (IBSAL), Centre for Environmental Studies and Rural Dynamization (CEADIR), University of Salamanca, 37007 Salamanca, Spain
2
Department of Physiology and Pharmacology, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain
*
Author to whom correspondence should be addressed.
Animals 2024, 14(23), 3371; https://doi.org/10.3390/ani14233371
Submission received: 28 October 2024
/
Revised: 18 November 2024
/
Accepted: 20 November 2024
/
Published: 22 November 2024
(This article belongs to the Section Companion Animals)
Simple Summary
Cardiopulmonary dirofilariosis is a chronic and potentially fatal vascular and pulmonary disease caused by Dirofilaria immitis, mainly affecting canids and felids. The disease is exacerbated by the production of thrombi following the death of the adult worms naturally or by adulticidal treatment. However, D. immitis is able to live for years in the host. Its excretory/secretory antigen (DiES) has been shown to interact with angiogenesis, a mechanism by which the host is able to form new blood vessels from existing ones. Our aim was to analyze the effect of the recombinant proteins actin (rDiAct) and fructose-bisphosphate aldolase (rDiFBAL), belonging to DiES, together with VEGF-A (angiogenic precursor) on the angiogenic process in an in vitro model of endothelial cells. The production of both pro- and antiangiogenic molecules was analyzed, as well as the cellular processes of cell proliferation and migration, and the formation of pseudocapillaries. Both rDiAct + VEGF-A and rDiFBAL + VEGF-A stimulate proangiogenic and cellular processes associated with the proangiogenic process. These results seem to indicate that D. immitis is able to stimulate specific molecules within its excretory/secretory antigen that aids its survival in the host vascular system.
Abstract
Heartworm disease, caused by Dirofilaria immitis, is a vector-borne zoonotic disease, (mainly affecting canids and felids) causing chronic vascular and pulmonary pathology in its early stages, which worsens with parasite load and/or death of adult worms in the pulmonary artery or right heart cavity, and can be fatal to the host. Angiogenesis is a mechanism by which new blood vessels are formed from existing ones. The aim of this work was to study the effect of two molecules of the D. immitis excretory/secretory antigen (DiES) on the angiogenic process, taking into account that this antigen is able to interact with this process and use it as a survival mechanism. For this purpose, an in vitro model of endothelial cells was used and treated with two recombinant proteins, i.e., actin (Act) and fructose-bisphosphate aldolase (FBAL) proteins belonging to DiES, and both pro- and antiangiogenic molecules were analyzed, as well as the cellular processes of cell proliferation, migration, and pseudocapillary formation. Act and FBAL proteins, together with vascular endothelial growth factor (VEGF-A), as an angiogenic precursor, are able to stimulate the production of proangiogenic factors as well as cellular processes of proliferation, migration, and pseudocapillary formation. This implies that these molecules could be produced by D. immitis to facilitate its survival, and the relationship between parasite and canine host would be further elaborated.
