Vericiguat attenuates doxorubicin-induced cardiotoxicity through the PRKG1/PINK1/STING axis

被引:1
作者
Zeng, Xianghui [1 ,2 ,5 ]
Zhang, Hao [1 ,2 ]
Xu, Tianyu [3 ]
Mei, Xiyuan [1 ,2 ]
Wang, Xiao [1 ,2 ]
Yang, Qiling [1 ,2 ]
Luo, Zhen [1 ,2 ]
Zeng, Qingchun [1 ,2 ]
Xu, Dingli [1 ,2 ]
Ren, Hao [2 ,4 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Cardiol, State Key Lab Organ Failure Res, Guangzhou, Peoples R China
[2] Minist Educ Peoples Republ China, Key Lab Organ Failure Res, Guangzhou, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Cardiol, NHC Key Lab Assisted Circulat, Guangzhou 510080, Peoples R China
[4] Southern Med Univ, Nanfang Hosp, Dept Rheumatol, Guangzhou, Peoples R China
[5] Ganzhou Hosp Tradit Chinese Med, Dept Cardiol, Ganzhou, Jiangxi, Peoples R China
关键词
Vericiguat; Doxorubicin; Cardiotoxicity; Inflammation; Mitochondrial dysfunction; SOLUBLE GUANYLATE-CYCLASE; INDUCED CARDIAC INJURY; INFLAMMATION; PATHWAY; LIVER;
D O I
10.1016/j.trsl.2024.07.005
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Doxorubicin (DOX) is restricted due to its severe cardiotoxicity. There is still a lack of viable and effective drugs to prevent or treat DOX-induced cardiotoxicity(DIC). Vericiguat is widely used to treat heart failure with reduced ejection fraction. However, it is not clear whether vericiguat can improve DIC. In the present study, we constructed a DIC model using mice and neonatal rat cardiomyocytes and found that vericiguat ameliorated DOXinduced cardiac insufficiency in mice, restored DOX-induced mitochondrial dysfunction in neonatal rat cardiomyocytes, and inhibited the expression of inflammatory factors. Further studies showed that vericiguat improved mitochondrial dysfunction and reduced mtDNA leakage into the cytoplasm by up-regulating PRKG1, which activated PINK1 and then inhibited the STING/IRF3 pathway to alleviate DIC. These findings demonstrate for the first time that vericiguat has therapeutic potential for the treatment of DIC.
引用
收藏
页码:90 / 103
页数:14
相关论文
共 52 条
  • [1] Cardioprotective effects of melatonin and metformin against doxorubicin-induced cardiotoxicity in rats are through preserving mitochondrial function and dynamics
    Arinno, Apiwan
    Maneechote, Chayodom
    Khuanjing, Thawatchai
    Ongnok, Benjamin
    Prathumsap, Nanthip
    Chunchai, Titikorn
    Arunsak, Busarin
    Kerdphoo, Sasiwan
    Shinlapawittayatorn, Krekwit
    Chattipakorn, Siriporn C.
    Chattipakorn, Nipon
    [J]. BIOCHEMICAL PHARMACOLOGY, 2021, 192
  • [2] Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction
    Armstrong, Paul W.
    Pieske, Burkert
    Anstrom, Kevin J.
    Ezekowitz, Justin
    Hernandez, Adrian F.
    Butler, Javed
    Lam, Carolyn S. P.
    Ponikowski, Piotr
    Voors, Adriaan A.
    Jia, Gang
    McNulty, Steven E.
    Patel, Mahesh J.
    Roessig, Lothar
    Koglin, Joerg
    O'Connor, Christopher M.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (20) : 1883 - 1893
  • [3] Soluble guanylate cyclase activator BAY 54-6544 improves vasomotor function and survival in an accelerated ageing mouse model
    Ataabadi, Ehsan Ataei
    Golshiri, Keivan
    Juettner, Annika A.
    de Vries, Rene
    Van den Berg-Garrelds, Ingrid
    Nagtzaam, Nicole M. A.
    Khan, Hina N.
    Leijten, Frank P. J.
    Brandt, Renata M. C.
    Dik, Willem A.
    van der Pluijm, Ingrid
    Danser, A. H. Jan
    Sandner, Peter
    Roks, Anton J. M.
    [J]. AGING CELL, 2022, 21 (09)
  • [4] Regulation of Mitochondria-Associated Membranes (MAMs) by NO/sGC/PKG Participates in the Control of Hepatic Insulin Response
    Bassot, Arthur
    Chauvin, Marie-Agnes
    Bendridi, Nadia
    Ji-Cao, Jingwei
    Vial, Guillaume
    Monnier, Lea
    Bartosch, Birke
    Alves, Anais
    Cottet-Rousselle, Cecile
    Gouriou, Yves
    Rieusset, Jennifer
    Morio, Beatrice
    [J]. CELLS, 2019, 8 (11)
  • [5] Nitric oxide protects the heart from ischemia-induced apoptosis and mitochondrial damage via protein kinase G mediated blockage of permeability transition and cytochrome c release
    Borutaite, Vilmante
    Morkuniene, Ramune
    Arandarcikaite, Odeta
    Jekabsone, Aiste
    Barauskaite, Jurgita
    Brown, Guy C.
    [J]. JOURNAL OF BIOMEDICAL SCIENCE, 2009, 16
  • [6] Bronner Denise N, 2016, Bio Protoc, V6, DOI 10.21769/BioProtoc.1839
  • [7] Soluble guanylate cyclase stimulators in patients with heart failure with reduced ejection fraction across the risk spectrum
    Butler, Javed
    Usman, Muhammad Shariq
    Anstrom, Kevin J.
    Blaustein, Robert O.
    Bonaca, Marc P.
    Ezekowitz, Justin A.
    Freitas, Cecilia
    Lam, Carolyn S. P.
    Lewis, Eldrin F.
    Lindenfeld, JoAnn
    McMullan, Ciaran J.
    Mentz, Robert J.
    O'Connor, Christopher
    Rosano, Giuseppe M. C.
    Ines Saldarriaga, Clara
    Senni, Michele
    Udelson, James
    Voors, Adriaan A.
    Zannad, Faiez
    [J]. EUROPEAN JOURNAL OF HEART FAILURE, 2022, 24 (11) : 2029 - 2036
  • [8] HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα
    Di Rita, Anthea
    Peschiaroli, Angelo
    D'Acunzo, Pasquale
    Strobbe, Daniela
    Hu, Zehan
    Gruber, Jens
    Nygaard, Mads
    Lambrughi, Matteo
    Melino, Gerry
    Papaleo, Elena
    Dengjel, Jorn
    El Alaoui, Said
    Campanella, Michelangelo
    Doetsch, Volker
    Rogov, Vladimir V.
    Strappazzon, Flavie
    Cecconi, Francesco
    [J]. NATURE COMMUNICATIONS, 2018, 9
  • [9] Polychlorinated Biphenyl Quinone Induces Caspase 1-Mediated Pyroptosis through Induction of Pro-inflammatory HMGB1-TLR4-NLRP3-GSDMD Signal Axis
    Dong, Wenjing
    Zhu, Qiushuang
    Yang, Bingwei
    Qin, Qi
    Wang, Yawen
    Xia, Xiaomin
    Zhu, Xiaokang
    Liu, Zixuan
    Song, Erqun
    Song, Yang
    [J]. CHEMICAL RESEARCH IN TOXICOLOGY, 2019, 32 (06) : 1051 - 1057
  • [10] Pegylated Liposomal Doxorubicin A Review of its use in Metastatic Breast Cancer, Ovarian Cancer, Multiple Myeloma and AIDS-Related Kaposi's Sarcoma
    Duggan, Sean T.
    Keating, Gillian M.
    [J]. DRUGS, 2011, 71 (18) : 2531 - 2558