Home HOME General Physiology and Biophysics 2020 General Physiology and Biophysics Vol.39, No.2, 123–134, 2020

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Quarterly, 80 pp. per issue
Founded: 1982
ISSN  1338-4325 (online)

Published in English

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General Physiology and Biophysics Vol.39, No.2, 123–134, 2020

Title: PCSK9 promotes the secretion of pro-inflammatory cytokines by macrophages to aggravate H/R-induced cardiomyocyte injury via activating NF-κB signalling
Author: Cheng-Long Yang, Yi-Di Zeng, Zhi-Xi Hu, Hao Liang

Abstract: The upregulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) was reported to be involved in regulating the levels of inflammatory markers and apoptosis in macrophages. This study aims to investigate the function and regulation of PCSK9 in myocardial ischaemia. The results of our study showed dramatically increased expression of PCSK9 induced by hypoxia/reoxygenation (H/R) stress rather than by apoptosis in primary murine cardiomyocytes and HL-1 cells. Moreover, PCSK9 promoted H/R-induced pro-inflammatory cytokine release from macrophages, while silencing of PCSK9 inhibited the expression of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Additionally, PCSK9 facilitated the release of pro-inflammatory cytokines from macrophages under H/R conditions, which decreased cardiomyocyte viability and promoted apoptosis of cardiomyocytes. For the underlying mechanisms, we identified PCSK9-induced NF-κB activation as being involved in the cardiomyocyte apoptosis, which was blocked by the NF-κB inhibitor BAY 11-7082. Collectively, this study provides new insights into the therapeutic possibility of regulating PCSK9 in cardiomyocytes for the treatment of ischaemic cardiomyopathy.

Keywords: PCSK9 — Cardiomyocytes — Macrophages — Pro-inflammatory cytokines — NF-κB signalling
Published online: 26-Mar-2020
Year: 2020, Volume: 39, Issue: 2 Page From: 123, Page To: 134

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