Tags

Type your tag names separated by a space and hit enter

Klotho improves diabetic cardiomyopathy by suppressing the NLRP3 inflammasome pathway.
Life Sci. 2019 Oct 01; 234:116773.LS

Abstract

AIMS

NLRP3 inflammasome activation is essential for the development and prognosis of diabetic cardiomyopathy (DCM). The anti-aging protein Klotho is suggested to modulate tissue inflammatory responses. The aim of the present study was to examine the protective effects of Klotho on DCM.

MAIN METHODS

A streptozotocin-induced diabetes mouse model was established to assess the effects of Klotho in vivo, which was administered for 12 weeks. The characteristics of type 1 DCM were evaluated by general status, echocardiography, and histopathology. The expression of associated factors was determined by RT-qPCR and western blotting. Parallel experiments to determine the molecular mechanism through which Klotho prevents DCM were performed using H9C2 cells exposed to high glucose (35 mM).

KEY FINDINGS

Diabetes-induced increases in serum creatine kinase-muscle/brain and lactate dehydrogenase levels, cardiac fibrosis, cardiomyocyte apoptosis, and cardiac dysfunction were ameliorated by Klotho. Additionally, Klotho suppressed TXNIP expression, NLRP3 inflammasome activation, and expression of the inflammatory cytokines tumor necrosis factor ɑ, interleukin-1β, and interleukin-18 in vivo. In high glucose-cultured cardiomyocytes, Klotho and N-acetylcysteine significantly downregulated intracellular reactive oxygen species generation and TXNIP/NLRP3 inflammasome activation. Pretreatment of H9C2 cells with NLRP3 siRNA or Klotho prevented high glucose-induced inflammation and apoptosis in H9C2 cells.

SIGNIFICANCE

Our results demonstrate that the protective effect of Klotho on diabetes-induced cardiac injury is associated with inhibition of the NLRP3 inflammasome pathway, suggesting its therapeutic potential for DCM.

Authors+Show Affiliations

Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, China.Grade 2016 Class 2, The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China.Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, China; Department of Cardiology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address: libingong08@163.com.Department of Orthopedics, Qingdao Municipal Hospital, Qingdao, Shandong 266011, China.Department of Cardiology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31422095

Citation

Li, Xuelian, et al. "Klotho Improves Diabetic Cardiomyopathy By Suppressing the NLRP3 Inflammasome Pathway." Life Sciences, vol. 234, 2019, p. 116773.
Li X, Li Z, Li B, et al. Klotho improves diabetic cardiomyopathy by suppressing the NLRP3 inflammasome pathway. Life Sci. 2019;234:116773.
Li, X., Li, Z., Li, B., Zhu, X., & Lai, X. (2019). Klotho improves diabetic cardiomyopathy by suppressing the NLRP3 inflammasome pathway. Life Sciences, 234, 116773. https://doi.org/10.1016/j.lfs.2019.116773
Li X, et al. Klotho Improves Diabetic Cardiomyopathy By Suppressing the NLRP3 Inflammasome Pathway. Life Sci. 2019 Oct 1;234:116773. PubMed PMID: 31422095.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Klotho improves diabetic cardiomyopathy by suppressing the NLRP3 inflammasome pathway. AU - Li,Xuelian, AU - Li,Zhiyang, AU - Li,Bingong, AU - Zhu,Xianjie, AU - Lai,Xingjun, Y1 - 2019/08/15/ PY - 2019/04/20/received PY - 2019/08/01/revised PY - 2019/08/14/accepted PY - 2019/8/20/pubmed PY - 2019/9/21/medline PY - 2019/8/19/entrez KW - Diabetic cardiomyopathy KW - Klotho KW - NLRP3 SP - 116773 EP - 116773 JF - Life sciences JO - Life Sci VL - 234 N2 - AIMS: NLRP3 inflammasome activation is essential for the development and prognosis of diabetic cardiomyopathy (DCM). The anti-aging protein Klotho is suggested to modulate tissue inflammatory responses. The aim of the present study was to examine the protective effects of Klotho on DCM. MAIN METHODS: A streptozotocin-induced diabetes mouse model was established to assess the effects of Klotho in vivo, which was administered for 12 weeks. The characteristics of type 1 DCM were evaluated by general status, echocardiography, and histopathology. The expression of associated factors was determined by RT-qPCR and western blotting. Parallel experiments to determine the molecular mechanism through which Klotho prevents DCM were performed using H9C2 cells exposed to high glucose (35 mM). KEY FINDINGS: Diabetes-induced increases in serum creatine kinase-muscle/brain and lactate dehydrogenase levels, cardiac fibrosis, cardiomyocyte apoptosis, and cardiac dysfunction were ameliorated by Klotho. Additionally, Klotho suppressed TXNIP expression, NLRP3 inflammasome activation, and expression of the inflammatory cytokines tumor necrosis factor ɑ, interleukin-1β, and interleukin-18 in vivo. In high glucose-cultured cardiomyocytes, Klotho and N-acetylcysteine significantly downregulated intracellular reactive oxygen species generation and TXNIP/NLRP3 inflammasome activation. Pretreatment of H9C2 cells with NLRP3 siRNA or Klotho prevented high glucose-induced inflammation and apoptosis in H9C2 cells. SIGNIFICANCE: Our results demonstrate that the protective effect of Klotho on diabetes-induced cardiac injury is associated with inhibition of the NLRP3 inflammasome pathway, suggesting its therapeutic potential for DCM. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/31422095/Klotho_improves_diabetic_cardiomyopathy_by_suppressing_the_NLRP3_inflammasome_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(19)30700-3 DB - PRIME DP - Unbound Medicine ER -