Depletion of β3-adrenergic receptor relieves pressure overload-induced cardiac hypertrophy and heart failure via enhancing innate immune response - 09/10/21
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Abstract |
Cardiac pressure overload is a crucial risk factor for cardiac hypertrophy and heart failure. Our previous study showed that depletion of the β3-adrenergic receptor (ADRB3) induced left ventricular diastolic dysfunction via potential regulation of energy metabolism and cardiac contraction. However, the effects of ADRB3 on pressure overload-induced heart failure remain unclear. In the present study, systemic ADRB3-knockout mice suffering from transverse aortic constriction (TAC) surgery were used to identify the effects of ADRB3 on pressure overload-induced heart failure. Compared to wild-type mice, ADRB3 depletion significantly improved the left ventricular ejection fraction, reduced left ventricular posterior wall thickness and interventricular septum thickness, and decreased the area of cardiomyocytes after TAC. RNA sequencing and bioinformatics analysis showed that ADRB3 depletion up-regulated 275 mRNAs and down-regulated 105 mRNAs in mice suffering TAC surgery. GO analysis, GO-tree analysis, and GSEA showed that ADRB3 depletion mainly enhanced the innate immune response of hearts in cardiac pressure overload mice. In addition, pathway analysis and Pathway-Act analysis presented that innate immune response-related pathways, including RIG-I-like receptor signaling pathway, antigen processing and presentation, Toll-like receptor signaling pathway, and cell adhesion molecules, were significantly enriched in ADRB3-KO-TAC mice. Ten hub genes were identified using protein-protein interaction network, MCODE, and cytoHubba analysis. Furthermore, the depletion and activation of ADRB3 validated the effects of ADRB3 on the innate immune response of hearts after TAC. In conclusion, ADRB3 depletion relieves pressure overload-induced cardiac hypertrophy and heart failure, and these effects could be explained by the enhancement of innate immune response.
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Highlights |
• | ADRB3 depletion relieved cardiac hypertrophy and heart failure in TAC mice. |
• | RNA sequencing was performed to detect dysregulated mRNAs in ADRB3-KO-TAC mice. |
• | ADRB3 depletion mainly enhanced the innate immune response of hearts in TAC mice. |
• | Ten hub genes were identified with PPI network, MCODE, and cytoHubba analysis. |
Keywords : β3-adrenergic receptor, Heart failure, Cardiac hypertrophy, Innate immune response
Plan
Vol 143
Article 112194- novembre 2021 Retour au numéro
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