NLRP3-mediated pyroptosis aggravates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction in mice: cardioprotective role of irisin
Autor: | Mingming Lv, Xiaobo Wang, Rongchuan Yue, Yulong Zhang, Qingqing Tan, Zaiyong Zheng, Dan Qin, Tao Wang, Houxiang Hu, Yu Luo |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty Immunology Inflammation lcsh:RC254-282 Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation Fibrosis Internal medicine Myokine medicine lcsh:QH573-671 Pressure overload integumentary system business.industry lcsh:Cytology Pyroptosis Inflammasome Cell Biology medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Angiotensin II Cardiovascular diseases 030104 developmental biology Endocrinology cardiovascular system Clinical pharmacology medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Cell Death Discovery, Vol 7, Iss 1, Pp 1-11 (2021) Cell Death Discovery |
ISSN: | 2058-7716 |
Popis: | The exact mechanism of myocardial hypertrophy has not been completely elucidated. NOD-like receptor protein 3 (NLRP3) and the pyroptotic cascade play a critical role in cardiac hypertrophy and inflammation. The myokine irisin can inhibit NLRP3 activation, although its exact mechanism of action is unknown. In this study, we induced cardiac hypertrophy in a mouse model via aortic constriction (TAC) to further explore the pathological role of NLRP3 inflammasome-mediated pyroptosis and the potential therapeutic effects of irisin. Cardiac hypertrophy significantly increased the percentage of apoptotic cells and upregulated IL-1β, cleaved caspase-1, and GSDMD-N that lie downstream of the NLRP3 inflammasome. Subsequently, irisin was co-administered to the TAC mice or angiotensin II (Ang-II)-treated cardiomyocytes to observe whether it could attenuate pyroptosis and cardiac hypertrophy. We established a direct association between pyroptosis and cardiac hypertrophy and found that pharmacological or genetic inhibition of NLRP3 attenuated cardiac hypertrophy. Furthermore, ectopic overexpression of NLRP3 abrogated the cardioprotective effects of irisin. To summarize, pyroptosis is a pathological factor in cardiac hypertrophy, and irisin is a promising therapeutic agent that inhibits NLRP3-mediated pyroptosis of cardiomyocytes. |
Databáze: | OpenAIRE |
Externí odkaz: |