AUTHOR=Liu Jixiang , Chang Ziyi , Zhang Zhu , Wang Bei , Xie Wanmu , Gao Qian , Zhang Shuai , Zhang Yunxia , Tian Han , Fu Zhihui , Li Yishan , Zhen Kaiyuan , Ma Shuangshuang , Zhong Dingrong , Yang Peiran , Zhai Zhenguo 

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1023282

DOI=10.3389/fcvm.2022.1023282

ISSN=2297-055X

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 of interventions, but they have not been investigated.
Methods: We collected pulmonary endarterectomy (PEA) samples of CTEPH patients from December 2016 to August 2021. Following detailed pathological examination of the PEA specimen, CTEPH patients were divided into two age- and sex-matched groups, those with and without atherosclerotic lesion (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, had a longer timespan between embolism and PEA surgery, and a lower rate of residual pulmonary hypertension post-PEA than those without atherosclerotic lesion, whereas the classic risk factors of arterial atherosclerosis, such as smoking and altered blood lipids, 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.