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Abnormal apelin-ACE2 and SGLT2 signaling contribute to adverse cardiorenal injury in patients with COVID-19.
Li, Xue-Ting; Zhang, Mi-Wen; Zhang, Zhen-Zhou; Cao, Yu-Dan; Liu, Xiao-Yan; Miao, Ran; Xu, Yuan; Song, Xiao-Fang; Song, Jia-Wei; Liu, Ying; Xu, Ying-Le; Li, Jing; Dong, Ying; Zhong, Jiu-Chang.
  • Li XT; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Zhang MW; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Zhang ZZ; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; State Key Laboratory of Medical Genomics & Shanghai Instit
  • Cao YD; Department of endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Liu XY; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Miao R; Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Xu Y; Department of endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Song XF; Department of endocrinology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Song JW; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Liu Y; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Xu YL; State Key Laboratory of Medical Genomics & Shanghai Institute of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
  • Li J; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Dong Y; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • Zhong JC; Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; Medical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China; State Key Laboratory of Medical Genomics & Shanghai Instit
Int J Cardiol ; 336: 123-129, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1230514
ABSTRACT

BACKGROUND:

Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent response for novel coronavirus disease 2019 (COVID-19). This study aimed to explore the roles of ACE2, apelin and sodium-glucose cotransporter 2 (SGLT2) in SARS-CoV-2-mediated cardiorenal damage. METHODS AND

RESULTS:

The published RNA-sequencing datasets of cardiomyocytes infected with SARS-CoV-2 and COVID-19 patients were used. String, UMAP plots and single cell RNA sequencing data were analyzed to show the close relationship and distinct cardiorenal distribution patterns of ACE2, apelin and SGLT2. Intriguingly, there were decreases in ACE2 and apelin expression as well as marked increases in SGLT2 and endothelin-1 levels in SARS-CoV-2-infected cardiomyocytes, animal models with diabetes, acute kidney injury, heart failure and COVID-19 patients. These changes were linked with downregulated levels of interleukin (IL)-10, superoxide dismutase 2 and catalase as well as upregulated expression of profibrotic genes and pro-inflammatory cytokines/chemokines. Genetic ACE2 deletion resulted in upregulation of pro-inflammatory cytokines containing IL-1ß, IL-6, IL-17 and tumor necrosis factor α. More importantly, dapagliflozin strikingly alleviated cardiorenal fibrosis in diabetic db/db mice by suppressing SGLT2 levels and potentiating the apelin-ACE2 signaling.

CONCLUSION:

Downregulation of apelin and ACE2 and upregulation of SGLT2, endothelin-1 and pro-inflammatory cytokines contribute to SARS-CoV-2-mediated cardiorenal injury, indicating that the apelin-ACE2 signaling and SGLT2 inhibitors are potential therapeutic targets for COVID-19 patients.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Limits: Animals / Humans Language: English Journal: Int J Cardiol Year: 2021 Document Type: Article Affiliation country: J.ijcard.2021.05.029

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Limits: Animals / Humans Language: English Journal: Int J Cardiol Year: 2021 Document Type: Article Affiliation country: J.ijcard.2021.05.029