Caspase-1 as Molecular Key in Cardiac Remodeling during Cardiorenal Syndrome Type 3 in the Murine Model

Author(s): Mayra Trentin-Sonoda, Frayli Maltoni Fratoni, Carolina Victoria da Cruz Junho, Wellington Caio Silva, Karine Panico, Marcela Sorelli Carneiro-Ramos*.

Journal Name: Current Molecular Medicine

Volume 20 , Issue 1 , 2020

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Abstract:

Background: Renal ischemia/reperfusion induces a systemic inflammatory response that is directly related to the development of cardiac hypertrophy due to cardiorenal syndrome type 3. Classic inflammatory pathways have been extensively investigated in cardiovascular diseases, including the participation of inflammasome in caspase-1-dependent IL-1β cleavage.

Objective: In this study, we aimed to understand how lack of caspase-1 would impact the hypertrophic and apoptotic response in the heart after renal ischemia/reperfusion.

Methods: Wildtype and caspase-1 knockout animals were submitted to a renal ischemia/reperfusion protocol. Briefly, left kidney ischemia was induced in male C57BL/6 mice for 60 min, followed by reperfusion for 15 days. Gene expression was analysed by Real-Time PCR. Caspase activity was also evaluated.

Results: Lack of caspase-1 led to a more pronounced cardiac hypertrophy in mice subjected to renal ischemia-reperfusion. Such hypertrophic process was accompanied by increased activity of caspase3/7 and 9, indicating apoptosis initiation in an IL-1β- independent manner.

Conclusion: Our data corroborate important findings on the role of caspase-1 in the development of cardiac hypertrophy and remodeling.

Keywords: Apoptosis, renal injury, cardiac hypertrophy, caspase-1, inflammation, cardiorenal syndrome.

[1]
Liu D, Shang H, Liu Y. Stanniocalcin-1 Protects a Mouse Model from Renal Ischemia-Reperfusion Injury by Affecting ROS-Mediated Multiple Signaling Pathways. Int J Mol Sci 2016; 17(7)E1051
[http://dx.doi.org/10.3390/ijms17071051] [PMID: 27420048]
[2]
Saparov A, Ogay V, Nurgozhin T, et al. Role of the immune system in cardiac tissue damage and repair following myocardial infarction. Inflamm Res 2017; 66(9): 739-51.
[http://dx.doi.org/10.1007/s00011-017-1060-4] [PMID: 28600668]
[3]
Akchurin OM, Kaskel F. Update on inflammation in chronic kidney disease. Blood Purif 2015; 39(1-3): 84-92.
[http://dx.doi.org/10.1159/000368940] [PMID: 25662331]
[4]
Merkle S, Frantz S, Schön MP, et al. A role for caspase-1 in heart failure. Circ Res 2007; 100(5): 645-53.
[http://dx.doi.org/10.1161/01.RES.0000260203.55077.61] [PMID: 17303764]
[5]
Scarpioni R, Obici L. Renal Involvement in Autoinflammatory Diseases and Inflammasome-Mediated Chronic Kidney Damage Clin Exp Rheumatol 2018; 36 Suppl 110(1): 54-60.
[6]
Rojas A, Kong SW, Agarwal P, Gilliss B, Pu WT, Black BL. GATA4 is a direct transcriptional activator of cyclin D2 and Cdk4 and is required for cardiomyocyte proliferation in anterior heart field-derived myocardium. Mol Cell Biol 2008; 28(17): 5420-31.
[http://dx.doi.org/10.1128/MCB.00717-08] [PMID: 18591257]
[7]
Aries A, Whitcomb J, Shao W, Komati H, Saleh M, Nemer M. Caspase-1 cleavage of transcription factor GATA4 and regulation of cardiac cell fate. Cell Death Dis 2014; 5e: 1566.
[http://dx.doi.org/10.1038/cddis.2014.524] [PMID: 25501827]
[8]
Trentin-Sonoda M, da Silva RC, Kmit FV, et al. Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-Induced Cardiac Hypertrophy in Mice. PLoS One 2015; 10(10)e0139350
[http://dx.doi.org/10.1371/journal.pone.0139350] [PMID: 26448184]
[9]
Cirino-Silva R, Kmit FV, Trentin-Sonoda M, et al. Renal ischemia/reperfusion-induced cardiac hypertrophy in mice: Cardiac morphological and morphometric characterization. JRSM Cardiovasc Dis 2017.62048004016689440
[http://dx.doi.org/10.1177/2048004016689440] [PMID: 28228941]
[10]
Luo P, Dong G, Liu L, Zhou H. The Long-Term Consumption of Ginseng Extract Reduces the Susceptibility of Intermediate-Aged Hearts to Acute Ischemia Reperfusion Injury. PLoS One 2015; 10(12)e0144733
[http://dx.doi.org/10.1371/journal.pone.0144733] [PMID: 26650753]
[11]
Alarcon MML, Trentin-Sonoda M, Panico K, et al. Cardiac arrhythmias after renal I/R depend on IL-1β. J Mol Cell Cardiol 2019; 131: 101-11.
[http://dx.doi.org/10.1016/j.yjmcc.2019.04.025] [PMID: 31029578]
[12]
Ioannou K, Stel VS, Dounousi E, et al. Inflammation, Endothelial Dysfunction and Increased Left Ventricular Mass in Chronic Kidney Disease (CKD) Patients: A Longitudinal Study. PLoS One 2015; 10(9)e0138461
[http://dx.doi.org/10.1371/journal.pone.0138461] [PMID: 26398099]
[13]
Kim B, Srivastava SK, Kim SH. Caspase-9 as a therapeutic target for treating cancer. Expert Opin Ther Targets 2015; 19(1): 113-27.
[http://dx.doi.org/10.1517/14728222.2014.961425] [PMID: 25256701]
[14]
Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35(4): 495-516.
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[15]
Tamamori-Adachi M, Ito H, Nobori K, et al. Expression of cyclin D1 and CDK4 causes hypertrophic growth of cardiomyocytes in culture: a possible implication for cardiac hypertrophy. Biochem Biophys Res Commun 2002; 296(2): 274-80.
[http://dx.doi.org/10.1016/S0006-291X(02)00854-9] [PMID: 12163013]
[16]
Zhong W, Mao S, Tobis S, et al. Hypertrophic growth in cardiac myocytes is mediated by Myc through a Cyclin D2-dependent pathway. EMBO J 2006; 25(16): 3869-79.
[http://dx.doi.org/10.1038/sj.emboj.7601252] [PMID: 16902412]


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VOLUME: 20
ISSUE: 1
Year: 2020
Page: [72 - 78]
Pages: 7
DOI: 10.2174/1566524019666190916153257
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