Pathological mechanism of heart failure with preserved ejection fraction in rats based on iTRAQ technology

Abstract

Objective Heart failure with preserved ejection fraction (HFpEF) is a public health problem worldwide. Treatments for the patients with HFpEF are not satisfactory because there is no unified understanding of the pathological mechanism of HFpEF. This study aims at investigating the potential pathological mechanism for the effective diagnosis and treatment of HFpEF. Methods Ten adult male Dahl salt sensitive rats (180–200 g) were divided into control and model groups. The rats in model group were fed with high salt diet (8% NaCl) to induce HFpEF for this comparative study. Behavioral changes, biochemical parameters, and histopathological changes of the rats were detected. iTRAQ technology combined with bioinformatics analysis was employed to study the differentially expressed proteins (DEPs) and their enrichment in signaling pathways. Results Echocardiography detection showed decreased LVEF, indicating impaired cardiac function (P < 0.01), increased LVPWd, indicating ventricular wall hypertrophy (P < 0.05), prolonged duration of IVRT and decreased E/A ratio, indicating diastolic dysfunction (P < 0.05) of the rats in model group. 563 DEPs were identified in the rats of both groups, with 243 up-regulated and 320 down-regulated. The expression of PPAR signaling pathway in the rats of model group was down-regulated, with PPARα most significantly decreased (91.2%) (P < 0.01), PPARγ obviously decreased (63.60%) (P < 0.05), and PPARβ/δ decreased (45.33%) (P < 0.05). The DEPs enriched in PPAR signaling pathway were mainly related to such biological processes as fatty acid beta-oxidation, such cellular components as peroxisome, and such molecular functions as lipid binding. Conclusions NaCl high salt diet is one of the factors to increase the incidence of HFpEF in rats. PPARα, PPARγ and PPAR β/δ might be the targets of HFpEF. The findings may provide a theoretical basis for the treatment of HFpEF in clinical practice.