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The Angiostrongylus vasorum excretory/secretory proteome contains putative modulators of the host coagulation

ABSTRACT: Angiostrongylus vasorum is a cardiopulmonary nematode of canids and is, among others associated with bleeding disorders in dogs. The pathogenesis of coagulopathies remains unclear. We performed a deep proteomic characterization of sex specific A. vasorum excretory/secretory proteins (ESP) and of cuticular surface proteins, and evaluated the effect of ESP on host coagulation and fibrinolysis in vitro. Proteins were quantified by liquid chromatography coupled to mass spectrometry and functionally characterized through gene ontology and pathway enrichment analysis. In total, we identified 1069 ESP (944 from female and 959 from male specimens) and 1195 surface proteins (705 and 1135, respectively). Among these, we identified putative modulators of host coagulation, e.g., von Willebrand factor type D domain protein orthologues as well as several proteases, including serine type proteases, protease inhibitors and proteasome subunits. The effect of ESP on dog coagulation and fibrinolysis was evaluated on canine endothelial cells and by rotational thromboelastometry (ROTEM). After stimulation with ESP, tissue factor and serpin E1 transcript expression increased. ROTEM revealed minimal interaction of ESP with dog blood and did not influence the onset of fibrinolysis. We thus conclude that Angiostrongylus vasorum ESP and surface proteins do not act alone in the induction of bleeding in dogs. The interaction with the host’s vascular haemostasis is limited. It is likely that coagulopathies in A. vasorum infected dogs are the result of a multifactorial response of the host to this parasitic infection.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Angiostrongylus Vasorum

SUBMITTER: Nina Gillis

LAB HEAD: Manuela Schnyder

PROVIDER: PXD027520 | Pride | 2021-11-03

REPOSITORIES: Pride

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			Action	DRS
	20181116_010_S186433_ES_female_1_Group_1.raw	Raw
	20181116_011_S186436_ES_male_4_Group_2.raw	Raw
	20181116_012_S186437_ES_male_5_Group_2.raw	Raw
	20181116_014_S186434_ES_female_2_Group_1.raw	Raw
	20190213_121901_20190213_DIA_Acant_Acost_ES.sne	Other

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Project description:Dogs are commonly used models of human inherited retinal disorders. Because the dog retina contains a macula-like region, dogs are susceptible to maculopathies with many shared genetic etiologies with humans. Human macular gene expression has been characterized and provides insight into the underlying basis of macular disease. We sought to compare macular gene expression profiles in dogs and humans and interrogate macular disease-associated genes for differential expression between macula and periphery. RNA sequencing was performed on 8mm samples of the dog macular region and superior peripheral region, sampling retina and retinal pigmented epithelium/choroid separately. Read sequences were mapped to CanFam3.1 and raw read counts were analyzed to determine significantly differentially expressed genes between macula and periphery within each tissue. A similar analytic pipeline was used with a published dataset of human samples to allow direct dog/human comparisons. Pathways and processes involved in significantly DEGs were identified using the Database for Annotation, Visualization and Integrated Discovery. Dogs and humans shared the extent and direction of macular retinal differential gene expression, with multiple shared biological pathways implicated in differential expression. There were fewer similarities between dog and human in the supporting tissues of the retina (the RPE, choroid, sclera). Many genes implicated in heritable retinal and macular disorders in both dogs and humans were differentially expressed between macula and periphery. Approximately 2/3 of genes associated with human age-related macular degeneration were differentially expressed in at least one human tissue, whereas approximately half were differentially expressed in at least one dog tissue. This work underpins the dog macular retinal region as analogous to the human macula in terms of differential gene expression. Whilst age-related maculopathy has not been described in dogs, evidence supports the study of aging of the macula and susceptibility to age-associated pathology in dogs.

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The Angiostrongylus vasorum excretory/secretory proteome contains putative modulators of the host coagulation

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