Qi deficiency syndrome in heart failure:integrative analysis reveals CISD2-linked lipid metabolic dysregulation and prognostic implicationsOA
Background:“Qi deficiency”(a pathological state where the body’s vital energy(Qi)is insufficient or weakened,impairing physiological functions and diminishing the body’s ability to perform daily activities,defend against illness,and maintain homeostasis)syndrome is considered a critical syndrome in traditional Chinese medicine(TCM)and is associated with poor prognosis in heart failure(HF).This study investigates the clinical,metabolic,and transcriptomic differences between heart failure patients with and without Qi deficiency syndrome.Methods:56 heart failure patients were evaluated using a Qi deficiency syndrome scale and divided into Qi deficiency syndrome(QD)and non-Qi deficiency(non-QD)groups based on the median score.Clinical characteristics,including baseline N-terminal pro-B-type natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),total diuretic use during hospitalization,and 90-day rehospitalization rates,were compared between the groups.Differentially expressed genes(DEGs)and differential metabolites were identified,followed by enrichment analyses and validation using qPCR and Western blot in AC16 cardiomyocytes.Results:QD patients exhibited significantly higher NT-proBNP levels,lower LVEF,and increased 90-day rehospitalization rates.Metabolomic profiling revealed lipid metabolism disruptions,notably in linoleic acid and phospholipid pathways.Transcriptomic analysis highlighted 17 DEGs,including CISD2,a critical mitochondrial regulator,which was downregulated in QD patients.Correlation analysis identified significant associations between DEGs(e.g.,CISD2,BPGM)and lipid metabolites such as PC(16:0/P-16:0).Functional knockdown of CISD2 in AC16 cells led to upregulation of lipid oxidation enzymes ALOX15 and CYP1A2,linking CISD2 dysfunction to lipid metabolic dysregulation.Conclusion:Qi deficiency is associated with more severe heart failure symptoms,worse prognosis,and distinct metabolic and transcriptomic profiles,particularly in lipid metabolism.CISD2 emerges as a potential therapeutic target,offering new avenues for integrating molecular insights with TCM approaches to optimize HF management.
Jia-Mei Huang;Lu-Hua Xu;Yu-Wen Qi;Jie-Ni Fang;Teng-Yang Zhai;Zhi-Cong Zeng;Hong-Cai Shang;Rong-Feng Yang;Feng-Xia Lin
Department of Cardiovascular,Shenzhen Bao’an Traditional Chinese Medicine Hospital,Guangzhou University of Chinese Medicine,Shenzhen 518100,China The Seventh Clinical Medical College,Guangzhou University of Chinese Medicine,Shenzhen 518100,ChinaDepartment of Cardiovascular,Shenzhen Bao’an Traditional Chinese Medicine Hospital,Guangzhou University of Chinese Medicine,Shenzhen 518100,China The Seventh Clinical Medical College,Guangzhou University of Chinese Medicine,Shenzhen 518100,ChinaDepartment of Cardiovascular,Shenzhen Bao’an Traditional Chinese Medicine Hospital,Guangzhou University of Chinese Medicine,Shenzhen 518100,China The Seventh Clinical Medical College,Guangzhou University of Chinese Medicine,Shenzhen 518100,ChinaDepartment of Cardiovascular,Shenzhen Bao’an Traditional Chinese Medicine Hospital,Guangzhou University of Chinese Medicine,Shenzhen 518100,China The Seventh Clinical Medical College,Guangzhou University of Chinese Medicine,Shenzhen 518100,ChinaThe Seventh Clinical Medical College,Guangzhou University of Chinese Medicine,Shenzhen 518100,ChinaDepartment of Cardiovascular,Shenzhen Bao’an Traditional Chinese Medicine Hospital,Guangzhou University of Chinese Medicine,Shenzhen 518100,China The Seventh Clinical Medical College,Guangzhou University of Chinese Medicine,Shenzhen 518100,ChinaKey Laboratory of Chinese Internal Medicine of MOE,Beijing University of Chinese Medicine,Beijing 100105,ChinaDivision of Cardiovascular Intensive Care(CICU),Cardiac and Vascular Center,The University of Hong Kong-Shenzhen Hospital,Shenzhen 518053,ChinaDepartment of Cardiovascular,Shenzhen Bao’an Traditional Chinese Medicine Hospital,Guangzhou University of Chinese Medicine,Shenzhen 518100,China The Seventh Clinical Medical College,Guangzhou University of Chinese Medicine,Shenzhen 518100,China
医药卫生
Qi deficiency syndromeheart failurelipid metabolismtranscriptomic alterationsCISD2
《Traditional Medicine Research》 2026 (4)
P.39-49,11
supported by the Sanming Project of Medicine in Shenzhen[SZZYSM202206001]National Natural Science Foundation of China[82004320 and 82374383]Natural Science Foundation of Guangdong Province of China[2022A1515011710 and 2022A1515010679]Shenzhen Science and Technology Innovation Committee[JCYJ20220530141407017 and JCYJ20240813153619026]2024 High-quality Development Research Project of Shenzhen Bao’an Public Hospital[YNXM2024078]and Shenzhen Bao’an Chinese Medicine Hospital Research Program[BAZYY20220702].
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