The Proteome of Circulating Large Extracellular Vesicles in Diabetes and Hypertension

Hypertension and diabetes induce vascular injury through processes that are not fully understood. Changes in extracellular vesicle (EV) composition could provide novel insights. Here, we examined the protein composition of circulating EVs from hypertensive, diabetic and healthy mice. EVs were isolat...

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Main Authors: Akram Abolbaghaei, Maddison Turner, Jean-François Thibodeau, Chet E. Holterman, Christopher R. J. Kennedy, Dylan Burger
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/5/4930
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author Akram Abolbaghaei
Maddison Turner
Jean-François Thibodeau
Chet E. Holterman
Christopher R. J. Kennedy
Dylan Burger
author_facet Akram Abolbaghaei
Maddison Turner
Jean-François Thibodeau
Chet E. Holterman
Christopher R. J. Kennedy
Dylan Burger
author_sort Akram Abolbaghaei
collection DOAJ
description Hypertension and diabetes induce vascular injury through processes that are not fully understood. Changes in extracellular vesicle (EV) composition could provide novel insights. Here, we examined the protein composition of circulating EVs from hypertensive, diabetic and healthy mice. EVs were isolated from transgenic mice overexpressing human renin in the liver (TtRhRen, hypertensive), OVE26 type 1 diabetic mice and wild-type (WT) mice. Protein content was analyzed using liquid chromatography–mass spectrometry. We identified 544 independent proteins, of which 408 were found in all groups, 34 were exclusive to WT, 16 were exclusive to OVE26 and 5 were exclusive to TTRhRen mice. Amongst the differentially expressed proteins, haptoglobin (HPT) was upregulated and ankyrin-1 (ANK1) was downregulated in OVE26 and TtRhRen mice compared with WT controls. Conversely, TSP4 and Co3A1 were upregulated and SAA4 was downregulated exclusively in diabetic mice; and PPN was upregulated and SPTB1 and SPTA1 were downregulated in hypertensive mice, compared to WT mice. Ingenuity pathway analysis identified enrichment in proteins associated with SNARE signaling, the complement system and NAD homeostasis in EVs from diabetic mice. Conversely, in EVs from hypertensive mice, there was enrichment in semaphroin and Rho signaling. Further analysis of these changes may improve understanding of vascular injury in hypertension and diabetes.
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spelling doaj.art-000df9d8ad184fd6a8b3e5ad876b13c22023-11-17T07:55:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01245493010.3390/ijms24054930The Proteome of Circulating Large Extracellular Vesicles in Diabetes and HypertensionAkram Abolbaghaei0Maddison Turner1Jean-François Thibodeau2Chet E. Holterman3Christopher R. J. Kennedy4Dylan Burger5Chronic Disease Program, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaChronic Disease Program, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaChronic Disease Program, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaChronic Disease Program, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaChronic Disease Program, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaChronic Disease Program, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, CanadaHypertension and diabetes induce vascular injury through processes that are not fully understood. Changes in extracellular vesicle (EV) composition could provide novel insights. Here, we examined the protein composition of circulating EVs from hypertensive, diabetic and healthy mice. EVs were isolated from transgenic mice overexpressing human renin in the liver (TtRhRen, hypertensive), OVE26 type 1 diabetic mice and wild-type (WT) mice. Protein content was analyzed using liquid chromatography–mass spectrometry. We identified 544 independent proteins, of which 408 were found in all groups, 34 were exclusive to WT, 16 were exclusive to OVE26 and 5 were exclusive to TTRhRen mice. Amongst the differentially expressed proteins, haptoglobin (HPT) was upregulated and ankyrin-1 (ANK1) was downregulated in OVE26 and TtRhRen mice compared with WT controls. Conversely, TSP4 and Co3A1 were upregulated and SAA4 was downregulated exclusively in diabetic mice; and PPN was upregulated and SPTB1 and SPTA1 were downregulated in hypertensive mice, compared to WT mice. Ingenuity pathway analysis identified enrichment in proteins associated with SNARE signaling, the complement system and NAD homeostasis in EVs from diabetic mice. Conversely, in EVs from hypertensive mice, there was enrichment in semaphroin and Rho signaling. Further analysis of these changes may improve understanding of vascular injury in hypertension and diabetes.https://www.mdpi.com/1422-0067/24/5/4930diabeteshypertensionvascularextracellular vesiclesmicroparticlesmicrovesicles
spellingShingle Akram Abolbaghaei
Maddison Turner
Jean-François Thibodeau
Chet E. Holterman
Christopher R. J. Kennedy
Dylan Burger
The Proteome of Circulating Large Extracellular Vesicles in Diabetes and Hypertension
International Journal of Molecular Sciences
diabetes
hypertension
vascular
extracellular vesicles
microparticles
microvesicles
title The Proteome of Circulating Large Extracellular Vesicles in Diabetes and Hypertension
title_full The Proteome of Circulating Large Extracellular Vesicles in Diabetes and Hypertension
title_fullStr The Proteome of Circulating Large Extracellular Vesicles in Diabetes and Hypertension
title_full_unstemmed The Proteome of Circulating Large Extracellular Vesicles in Diabetes and Hypertension
title_short The Proteome of Circulating Large Extracellular Vesicles in Diabetes and Hypertension
title_sort proteome of circulating large extracellular vesicles in diabetes and hypertension
topic diabetes
hypertension
vascular
extracellular vesicles
microparticles
microvesicles
url https://www.mdpi.com/1422-0067/24/5/4930
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