PMID- 37219522
OWN - NLM
STAT- MEDLINE
DCOM- 20230526
LR  - 20230721
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 37
IP  - 6
DP  - 2023 Jun
TI  - TRPA1 deficiency aggravates dilated cardiomyopathy by promoting S100A8 expression 
      to induce M1 macrophage polarization in rats.
PG  - e22982
LID - 10.1096/fj.202202079RR [doi]
AB  - Transient receptor potential ankyrin 1 (TRPA1) plays an important role in 
      different cardiovascular diseases. However, the role of TRPA1 in dilated 
      cardiomyopathy (DCM) remains unclear. Here, we aimed to investigate the role of 
      TRPA1 in DCM induced by doxorubicin (DOX) and explore its possible mechanisms. 
      GEO data were used to explore the expression of TRPA1 in DCM patients. DOX 
      (2.5 mg/kg/week, 6 weeks, i.p.) was used to induce DCM. Bone marrow-derived 
      macrophages (BMDMs) and neonatal rat cardiomyocytes (NRCMs) were isolated to 
      explore the role of TRPA1 in macrophage polarization, cardiomyocyte apoptosis, 
      and pyroptosis. In addition, DCM rats were treated with the TRPA1 activator, 
      cinnamaldehyde to explore the possibility of clinical translation. TRPA1 
      expression was increased in left ventricular (LV) tissue in DCM patients and 
      rats. TRPA1 deficiency aggravated the cardiac dysfunction, cardiac injury, and LV 
      remodeling in DCM rats. In addition, TRPA1 deficiency promoted the M1 macrophage 
      polarization, oxidative stress, cardiac apoptosis, and pyroptosis induced by DOX. 
      RNA-seq results showed that TRPA1 knockout promoted the expression of S100A8, an 
      inflammatory molecule that belongs to the family of Ca(2+) -binding S100 
      proteins, in DCM rats. Furthermore, S100A8 inhibition attenuated M1 macrophage 
      polarization in BMDMs isolated from TRPA1 deficiency rats. Recombinant S100A8 
      promoted the apoptosis, pyroptosis, and oxidative stress in primary 
      cardiomyocytes stimulated with DOX. Finally, TRPA1 activation via cinnamaldehyde 
      alleviated the cardiac dysfunction and reduced S100A8 expression in DCM rats. 
      Taken together, these results suggested that TRPA1 deficiency aggravates DCM by 
      promoting S100A8 expression to induce M1 macrophage polarization and cardiac 
      apoptosis.
CI  - (c) 2023 Federation of American Societies for Experimental Biology.
FAU - Wang, Menglong
AU  - Wang M
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Zhao, Mengmeng
AU  - Zhao M
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Zheng, Zihui
AU  - Zheng Z
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Pan, Wei
AU  - Pan W
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Zhang, Jishou
AU  - Zhang J
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Yin, Zheng
AU  - Yin Z
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Wei, Cheng
AU  - Wei C
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Xu, Yao
AU  - Xu Y
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
FAU - Wan, Jun
AU  - Wan J
AUID- ORCID: 0000-0003-4865-783X
AD  - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
AD  - Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.
AD  - Hubei Key Laboratory of Cardiology, Wuhan, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 7864XYD3JJ (Acrolein)
RN  - 0 (Calgranulin A)
RN  - SR60A3XG0F (cinnamaldehyde)
RN  - 0 (Cytoskeletal Proteins)
RN  - 80168379AG (Doxorubicin)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (Trpa1 protein, rat)
RN  - 0 (TRPA1 protein, human)
SB  - IM
EIN - FASEB J. 2023 Aug;37(8):e23065. PMID: 37477922
MH  - Animals
MH  - Rats
MH  - Acrolein
MH  - Calgranulin A
MH  - *Cardiomyopathy, Dilated
MH  - Cytoskeletal Proteins
MH  - Doxorubicin
MH  - Macrophages
MH  - Myocytes, Cardiac
MH  - TRPA1 Cation Channel
MH  - Humans
OTO - NOTNLM
OT  - S100A8
OT  - TRPA1
OT  - apoptosis
OT  - dilated cardiomyopathy
OT  - macrophage polarization
EDAT- 2023/05/23 13:06
MHDA- 2023/05/25 06:42
CRDT- 2023/05/23 10:33
PHST- 2023/05/02 00:00 [revised]
PHST- 2022/12/20 00:00 [received]
PHST- 2023/05/05 00:00 [accepted]
PHST- 2023/05/25 06:42 [medline]
PHST- 2023/05/23 13:06 [pubmed]
PHST- 2023/05/23 10:33 [entrez]
AID - 10.1096/fj.202202079RR [doi]
PST - ppublish
SO  - FASEB J. 2023 Jun;37(6):e22982. doi: 10.1096/fj.202202079RR.