Clinical features and metabolic reprogramming of atherosclerotic lesions in patients with chronic thromboembolic pulmonary hypertension

Front Cardiovasc Med. 2022 Nov 15:9:1023282. doi: 10.3389/fcvm.2022.1023282. eCollection 2022.

Authors

Jixiang Liu^{1

2

3

4

5}, Ziyi Chang⁶, Zhu Zhang^{1

3

4

5}, Bei Wang⁶, Wanmu Xie^{1

3

4

5}, Qian Gao^{1

3

4

5}, Shuai Zhang^{1

3

4

5}, Yunxia Zhang^{1

3

4

5}, Han Tian^{1

2

3

4

5}, Zhihui Fu^{1

2

3

4

5}, Yishan Li^{3

4

5

7}, Kaiyuan Zhen^{1

3

4

5}, Shuangshuang Ma^{1

3

4

5}, Dingrong Zhong², Peiran Yang^{3

4

5

8}, Zhenguo Zhai^{1

2

3

4

5}

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
² Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
³ National Center for Respiratory Medicine, Beijing, China.
⁴ Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China.
⁵ National Clinical Research Center for Respiratory Diseases, Beijing, China.
⁶ Department of Pathology, China-Japan Friendship Hospital, Beijing, China.
⁷ The First Clinical Medical College, Shanxi Medical University, Taiyuan, China.
⁸ State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.

Abstract

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) patients may present with atherosclerotic lesions in their pulmonary arteries, but their clinical characteristics remain unclear. The metabolic pathways associated with the atherosclerotic lesions may explain their occurrence and have implications for interventions, but they have not been investigated.

Methods: We collected pulmonary endarterectomy (PEA) samples of CTEPH patients from December 2016 to August 2021. Following a detailed pathological examination of the PEA specimen, the patients were divided into those with and without lesions, and age- and sex matching were performed subsequently using propensity score matching (n = 25 each). Metabolomic profiling was used to investigate the metabolites of the proximal lesions in the PEA specimens.

Results: In our study population, 27.2% of all PEA specimens were found to contain atherosclerotic lesions. CTEPH patients with atherosclerotic lesions were more likely to have a history of symptomatic embolism and had a longer timespan between embolism and surgery, whereas the classic risk factors of systemic and coronary circulation could not distinguish CTEPH patients with or without atherosclerotic lesions. Metabolomic profiling revealed that the formation of atherosclerotic lesions in CTEPH was closely related to altered glycine, serine, and threonine metabolic axes, possibly involved in cellular senescence, energy metabolism, and a proinflammatory microenvironment.

Conclusion: The occurrence of atherosclerotic lesions in the pulmonary arteries of CTEPH was associated with symptomatic thromboembolic history and prolonged disease duration. The results revealed a new link between atherosclerotic lesions and aberrant amino acid metabolism in the context of CTEPH for the first time. This study has characterized the clinical and metabolic profiles of this distinct group of CTEPH patients, providing new insights into disease pathogenesis and potential interventions.

Keywords: atherosclerosis; chronic thromboembolic pulmonary hypertension (CTEPH); metabolic reprogramming; pulmonary embolism; pulmonary endarterectomy (PEA).

Copyright © 2022 Liu, Chang, Zhang, Wang, Xie, Gao, Zhang, Zhang, Tian, Fu, Li, Zhen, Ma, Zhong, Yang and Zhai.