Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension

Xiaohan Qin; Chuxiang Lei; Li Yan; Haidan Sun; Xiaoyan Liu; Zhengguang Guo; Wei Sun; Xiaoxiao Guo; Quan Fang

doi:10.3389/fmolb.2022.834179

Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension

Front Mol Biosci. 2022 Jul 5:9:834179. doi: 10.3389/fmolb.2022.834179. eCollection 2022.

Authors

Xiaohan Qin¹, Chuxiang Lei¹, Li Yan², Haidan Sun³, Xiaoyan Liu³, Zhengguang Guo³, Wei Sun³, Xiaoxiao Guo¹, Quan Fang¹

Affiliations

¹ Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
² Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
³ Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.

Abstract

Right ventricular failure (RVF) is the independent and strongest predictor of mortality in pulmonary arterial hypertension (PAH), but, at present, there are no preventive and therapeutic strategies directly targeting the failing right ventricle (RV). The underlying mechanism of RV hypertrophy (RVH) and dysfunction needs to be explored in depth. In this study, we used myocardial proteomics combined with metabolomics to elucidate potential pathophysiological changes of RV remodeling in a monocrotaline (MCT)-induced PAH rat model. The proteins and metabolites extracted from the RV myocardium were identified using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). The bioinformatic analysis indicated that elevated intracellular Ca²⁺ concentrations and inflammation may contribute to myocardial proliferation and contraction, which may be beneficial for maintaining the compensated state of the RV. In the RVF stage, ferroptosis, mitochondrial metabolic shift, and insulin resistance are significantly involved. Dysregulated iron homeostasis, glutathione metabolism, and lipid peroxidation related to ferroptosis may contribute to RV decompensation. In conclusion, we depicted a proteomic and metabolomic profile of the RV myocardium during the progression of MCT-induced PAH, and also provided the insights for potential therapeutic targets facilitating the retardation or reversal of RV dysfunction in PAH.

Keywords: ferroptosis; metabolome; proteome; pulmonary arterial hypertension; right ventricular failure.