Frontiers in Cardiovascular Medicine (Nov 2022)
Clinical features and metabolic reprogramming of atherosclerotic lesions in patients with chronic thromboembolic pulmonary hypertension
- Jixiang Liu,
- Jixiang Liu,
- Jixiang Liu,
- Jixiang Liu,
- Jixiang Liu,
- Ziyi Chang,
- Zhu Zhang,
- Zhu Zhang,
- Zhu Zhang,
- Zhu Zhang,
- Bei Wang,
- Wanmu Xie,
- Wanmu Xie,
- Wanmu Xie,
- Wanmu Xie,
- Qian Gao,
- Qian Gao,
- Qian Gao,
- Qian Gao,
- Shuai Zhang,
- Shuai Zhang,
- Shuai Zhang,
- Shuai Zhang,
- Yunxia Zhang,
- Yunxia Zhang,
- Yunxia Zhang,
- Yunxia Zhang,
- Han Tian,
- Han Tian,
- Han Tian,
- Han Tian,
- Han Tian,
- Zhihui Fu,
- Zhihui Fu,
- Zhihui Fu,
- Zhihui Fu,
- Zhihui Fu,
- Yishan Li,
- Yishan Li,
- Yishan Li,
- Yishan Li,
- Kaiyuan Zhen,
- Kaiyuan Zhen,
- Kaiyuan Zhen,
- Kaiyuan Zhen,
- Shuangshuang Ma,
- Shuangshuang Ma,
- Shuangshuang Ma,
- Shuangshuang Ma,
- Dingrong Zhong,
- Peiran Yang,
- Peiran Yang,
- Peiran Yang,
- Peiran Yang,
- Zhenguo Zhai,
- Zhenguo Zhai,
- Zhenguo Zhai,
- Zhenguo Zhai,
- Zhenguo Zhai
Affiliations
- Jixiang Liu
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Jixiang Liu
- Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Jixiang Liu
- National Center for Respiratory Medicine, Beijing, China
- Jixiang Liu
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Jixiang Liu
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Ziyi Chang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
- Zhu Zhang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Zhu Zhang
- National Center for Respiratory Medicine, Beijing, China
- Zhu Zhang
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Zhu Zhang
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Bei Wang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
- Wanmu Xie
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Wanmu Xie
- National Center for Respiratory Medicine, Beijing, China
- Wanmu Xie
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Wanmu Xie
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Qian Gao
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Qian Gao
- National Center for Respiratory Medicine, Beijing, China
- Qian Gao
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Qian Gao
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Shuai Zhang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Shuai Zhang
- National Center for Respiratory Medicine, Beijing, China
- Shuai Zhang
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Shuai Zhang
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Yunxia Zhang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Yunxia Zhang
- National Center for Respiratory Medicine, Beijing, China
- Yunxia Zhang
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Yunxia Zhang
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Han Tian
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Han Tian
- Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Han Tian
- National Center for Respiratory Medicine, Beijing, China
- Han Tian
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Han Tian
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Zhihui Fu
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Zhihui Fu
- Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Zhihui Fu
- National Center for Respiratory Medicine, Beijing, China
- Zhihui Fu
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Zhihui Fu
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Yishan Li
- National Center for Respiratory Medicine, Beijing, China
- Yishan Li
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Yishan Li
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Yishan Li
- The First Clinical Medical College, Shanxi Medical University, Taiyuan, China
- Kaiyuan Zhen
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Kaiyuan Zhen
- National Center for Respiratory Medicine, Beijing, China
- Kaiyuan Zhen
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Kaiyuan Zhen
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Shuangshuang Ma
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Shuangshuang Ma
- National Center for Respiratory Medicine, Beijing, China
- Shuangshuang Ma
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Shuangshuang Ma
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Dingrong Zhong
- Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Peiran Yang
- National Center for Respiratory Medicine, Beijing, China
- Peiran Yang
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Peiran Yang
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- Peiran Yang
- 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
- Zhenguo Zhai
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China
- Zhenguo Zhai
- Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Zhenguo Zhai
- National Center for Respiratory Medicine, Beijing, China
- Zhenguo Zhai
- Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Zhenguo Zhai
- National Clinical Research Center for Respiratory Diseases, Beijing, China
- DOI
- https://doi.org/10.3389/fcvm.2022.1023282
- Journal volume & issue
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Vol. 9
Abstract
BackgroundChronic 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.MethodsWe 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.ResultsIn 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.ConclusionThe 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
- chronic thromboembolic pulmonary hypertension (CTEPH)
- pulmonary embolism
- atherosclerosis
- pulmonary endarterectomy (PEA)
- metabolic reprogramming
