PMID- 37861880
OWN - NLM
STAT- Publisher
LR  - 20231020
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
DP  - 2023 Oct 20
TI  - Hydrogen sulfide inhibits gene expression associated with aortic valve 
      degeneration by inducing NRF2-related pro-autophagy effect in human aortic valve 
      interstitial cells.
LID - 10.1007/s11010-023-04881-2 [doi]
AB  - Aortic valve stenosis (AS) is the most common valvular heart disease but there 
      are currently no effective medical treatments that can delay disease progression 
      due to a lack of knowledge of the precise pathophysiology. The expression of 
      sulfide: quinone oxidoreductase (SQOR) and nuclear factor erythroid 2-related 
      factor 2 (NRF2) was decreased in the aortic valve of AS patients. However, the 
      role of SQOR and NRF2 in the pathophysiology of AS has not been found. We 
      investigated the effects of hydrogen sulfide (H(2)S)-releasing compounds on 
      diseased aortic valve interstitial cells (AVICs) to explain the cellular 
      mechanism of SQOR and elucidate the medical value of H(2)S for AS treatment. 
      Sodium hydrosulfide (NaHS) treatment increased the expression of SQOR and NRF2 
      gene and consequently induced the NRF2 target genes, such as NAD(P)H quinone 
      dehydrogenase 1 and cystathionine gamma-lyase. In addition, NaHS dose-dependently 
      decreased the expression level of fibrosis and inflammation-related genes (MMP9, 
      TNF-alpha, IL6) and calcification-related genes (ALP, osteocalcin, RUNX2, COL1A1) in 
      human AVICs. Furthermore, NaHS activated the AMPK-mTOR pathway and inhibited the 
      PI3K-AKT pathway, resulting in a pro-autophagy effect in human AVICs. An NRF2 
      inhibitor, brusatol, attenuated NaHS-induced AMPK activation and decreased the 
      autophagy markers Beclin-1 and LC3AB, suggesting that the mechanism of action of 
      H(2)S is related to NRF2. In conclusion, H(2)S decreased gene expression levels 
      related to aortic valve degeneration and activated AMPK-mTOR-mediated 
      pro-autophagy function associated with NRF2 in human AVICs. Therefore, H(2)S 
      could be a potential therapeutic target for the development of AS treatment.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Song, Naaleum
AU  - Song N
AD  - Division of Cardiology, Heart Institute, Asan Medical Center, University of Ulsan 
      College of Medicine, Seoul, Republic of Korea.
AD  - Department of Medical Science, Asan Medical Center, Asan Medical Institute of 
      Convergence Science and Technology, University of Ulsan College of Medicine, 88 
      Olympic-ro 43 Gil, Songpa-gu, Seoul, 05505, Republic of Korea.
FAU - Yu, Jeong Eun
AU  - Yu JE
AD  - Division of Cardiology, Heart Institute, Asan Medical Center, University of Ulsan 
      College of Medicine, Seoul, Republic of Korea.
AD  - Department of Medical Science, Asan Medical Center, Asan Medical Institute of 
      Convergence Science and Technology, University of Ulsan College of Medicine, 88 
      Olympic-ro 43 Gil, Songpa-gu, Seoul, 05505, Republic of Korea.
FAU - Ji, Eunhye
AU  - Ji E
AD  - Division of Cardiology, Heart Institute, Asan Medical Center, University of Ulsan 
      College of Medicine, Seoul, Republic of Korea.
FAU - Choi, Kyoung-Hee
AU  - Choi KH
AD  - Division of Cardiology, Heart Institute, Asan Medical Center, University of Ulsan 
      College of Medicine, Seoul, Republic of Korea.
FAU - Lee, Sahmin
AU  - Lee S
AD  - Division of Cardiology, Heart Institute, Asan Medical Center, University of Ulsan 
      College of Medicine, Seoul, Republic of Korea. sahmin.lee@amc.seoul.kr.
AD  - Department of Medical Science, Asan Medical Center, Asan Medical Institute of 
      Convergence Science and Technology, University of Ulsan College of Medicine, 88 
      Olympic-ro 43 Gil, Songpa-gu, Seoul, 05505, Republic of Korea. 
      sahmin.lee@amc.seoul.kr.
LA  - eng
GR  - 2019R1I1A2A01060702/National Research Foundation of Korea/
GR  - 2022IF-0004/Asan Institute for Life Sciences, Asan Medical Center/
PT  - Journal Article
DEP - 20231020
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
SB  - IM
OTO - NOTNLM
OT  - Aortic stenosis
OT  - Autophagy
OT  - Hydrogen sulfide
OT  - Nuclear factor erythroid 2-related factor 2
OT  - Sulfide: quinone oxidoreductase
EDAT- 2023/10/20 12:42
MHDA- 2023/10/20 12:42
CRDT- 2023/10/20 11:11
PHST- 2023/07/01 00:00 [received]
PHST- 2023/10/07 00:00 [accepted]
PHST- 2023/10/20 12:42 [medline]
PHST- 2023/10/20 12:42 [pubmed]
PHST- 2023/10/20 11:11 [entrez]
AID - 10.1007/s11010-023-04881-2 [pii]
AID - 10.1007/s11010-023-04881-2 [doi]
PST - aheadofprint
SO  - Mol Cell Biochem. 2023 Oct 20. doi: 10.1007/s11010-023-04881-2.