Irbesartan ameliorates chronic mountain sickness in a rat model via the cholesterol metabolism: An iTRAQ -based proteomics analysis.

Abstract

OBJECTIVE:

To study the effects of irbesartan on pulmonary artery lesions in a rat model with chronic mountain sickness (CMS) and identify the biomarkers involved.

METHODS:

In this study, we used a rat model of CMS to evaluate the therapeutic effect of irbesartan by measuring pulmonary artery pressure and evaluating the histopathology of the pulmonary artery. We also used proteomics technology to identify differentially expressed proteins (DEPs) in the serum and performed bioinformatics analysis. Results were then verified by enzyme linked immunosorbent assay (ELISA) and immunohistochemistry (IHC).

RESULTS:

Irbesartan treatment induced a significant decrease (P < 0.05) in the pulmonary artery pressure of CMS rats. Histopathological and electron microscope further confirmed that high altitude hypoxia induced changes in the structure of the pulmonary artery tissue and caused ultrastructural lesions. Proteomics analysis identified 40 DEPs; bioinformatics analysis further revealed that the cholesterol metabolism pathway plays a crucial role in the occurrence of CMS. ELISA and IHC verified that several DEPs (Apo-A1, Apo-C1, Apo-E, IGF-1, Profilin1, and Col1a1) represent critical biological markers in pulmonary artery disease caused by CMS.

CONCLUSIONS:

Irbesartan significantly improved pulmonary artery damage in a rat model of CMS possibly by impacting on the cholesterol metabolism pathway and by reducing damage to vascular endothelial cells. Irbesartan also inhibited the expression levels of IGF-1, Profilin1 and Col1a1 to relieve pulmonary artery pressure and improve lung function by inhibiting vascular remodeling. Several proteins were identified as potential biomarkers of CMS, including Apo-A1, Apo-C1, Apo-E, IGF-1, Profilin1, and Col1a1.

• Authors: Yiliyaer Nijiati, Tao Yang, Mutalifu Aimaiti, Dilinuer Maimaitiyiming, Ainiwaer Aikemu
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 141 Pg. 111802 (Sep 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34147903 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Antihypertensive Agents
• Cholesterol
• Irbesartan

Topics

• Altitude Sickness (drug therapy, metabolism)
• Animals
• Antihypertensive Agents (pharmacology, therapeutic use)
• Cholesterol (metabolism)
• Chronic Disease (drug therapy)
• Irbesartan (pharmacology, therapeutic use)
• Protein Interaction Maps (drug effects, physiology)
• Proteomics (methods)
• Pulmonary Artery (drug effects, metabolism)
• Pulmonary Circulation (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Vascular Remodeling (drug effects, physiology)