Cargando…

PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid‐lowering effects

During acute cardiac ischaemia/reperfusion (I/R), an increased plasma proprotein convertase subtilisin/kexin 9 (PCSK9) level instigates inflammatory and oxidative processes within ventricular myocytes, resulting in cardiac dysfunction. Therefore, PCSK9 inhibitor (PCSK9i) might exert cardioprotection...

Descripción completa

Detalles Bibliográficos
Autores principales: Palee, Siripong, McSweeney, Christian M., Maneechote, Chayodom, Moisescu, Dalila M., Jaiwongkam, Thidarat, Kerdphoo, Sasiwan, Chattipakorn, Siriporn C., Chattipakorn, Nipon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815840/
https://www.ncbi.nlm.nih.gov/pubmed/31557388
http://dx.doi.org/10.1111/jcmm.14586
_version_ 1783463264910311424
author Palee, Siripong
McSweeney, Christian M.
Maneechote, Chayodom
Moisescu, Dalila M.
Jaiwongkam, Thidarat
Kerdphoo, Sasiwan
Chattipakorn, Siriporn C.
Chattipakorn, Nipon
author_facet Palee, Siripong
McSweeney, Christian M.
Maneechote, Chayodom
Moisescu, Dalila M.
Jaiwongkam, Thidarat
Kerdphoo, Sasiwan
Chattipakorn, Siriporn C.
Chattipakorn, Nipon
author_sort Palee, Siripong
collection PubMed
description During acute cardiac ischaemia/reperfusion (I/R), an increased plasma proprotein convertase subtilisin/kexin 9 (PCSK9) level instigates inflammatory and oxidative processes within ventricular myocytes, resulting in cardiac dysfunction. Therefore, PCSK9 inhibitor (PCSK9i) might exert cardioprotection against I/R injury. However, the effects of PCSK9i on the heart during I/R injury have not been investigated. The effects of PCSK9i given at different time‐points during I/R injury on left ventricular (LV) function were investigated. Male Wistar rats were subjected to cardiac I/R injury and divided into 3 treatment groups (n = 10/group): pre‐ischaemia, during ischaemia and upon onset of reperfusion. The treatment groups received PCSK9i (Pep2‐8, 10 μg/kg) intravenously. A control group (n = 10) received saline solution. During the I/R protocol, arrhythmia scores and LV function were determined. Then, the infarct size, mitochondrial function, mitochondrial dynamics and level of apoptosis were determined. PCSK9i given prior to ischaemia exerted cardioprotection through protection of cardiac mitochondrial function, decreased infarct size and improved LV function, compared with control. PCSK9i administered during ischaemia and upon the onset of reperfusion did not provide any of those benefits. PCSK9i administered before ischaemia exerts cardioprotection, as demonstrated by the attenuation of infarct size and cardiac arrhythmia during cardiac I/R injury. The attenuation is associated with improved mitochondrial function and connexin43 phosphorylation, leading to improved LV function.
format Online
Article
Text
id pubmed-6815840
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-68158402019-11-01 PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid‐lowering effects Palee, Siripong McSweeney, Christian M. Maneechote, Chayodom Moisescu, Dalila M. Jaiwongkam, Thidarat Kerdphoo, Sasiwan Chattipakorn, Siriporn C. Chattipakorn, Nipon J Cell Mol Med Original Articles During acute cardiac ischaemia/reperfusion (I/R), an increased plasma proprotein convertase subtilisin/kexin 9 (PCSK9) level instigates inflammatory and oxidative processes within ventricular myocytes, resulting in cardiac dysfunction. Therefore, PCSK9 inhibitor (PCSK9i) might exert cardioprotection against I/R injury. However, the effects of PCSK9i on the heart during I/R injury have not been investigated. The effects of PCSK9i given at different time‐points during I/R injury on left ventricular (LV) function were investigated. Male Wistar rats were subjected to cardiac I/R injury and divided into 3 treatment groups (n = 10/group): pre‐ischaemia, during ischaemia and upon onset of reperfusion. The treatment groups received PCSK9i (Pep2‐8, 10 μg/kg) intravenously. A control group (n = 10) received saline solution. During the I/R protocol, arrhythmia scores and LV function were determined. Then, the infarct size, mitochondrial function, mitochondrial dynamics and level of apoptosis were determined. PCSK9i given prior to ischaemia exerted cardioprotection through protection of cardiac mitochondrial function, decreased infarct size and improved LV function, compared with control. PCSK9i administered during ischaemia and upon the onset of reperfusion did not provide any of those benefits. PCSK9i administered before ischaemia exerts cardioprotection, as demonstrated by the attenuation of infarct size and cardiac arrhythmia during cardiac I/R injury. The attenuation is associated with improved mitochondrial function and connexin43 phosphorylation, leading to improved LV function. John Wiley and Sons Inc. 2019-09-26 2019-11 /pmc/articles/PMC6815840/ /pubmed/31557388 http://dx.doi.org/10.1111/jcmm.14586 Text en © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Palee, Siripong
McSweeney, Christian M.
Maneechote, Chayodom
Moisescu, Dalila M.
Jaiwongkam, Thidarat
Kerdphoo, Sasiwan
Chattipakorn, Siriporn C.
Chattipakorn, Nipon
PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid‐lowering effects
title PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid‐lowering effects
title_full PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid‐lowering effects
title_fullStr PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid‐lowering effects
title_full_unstemmed PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid‐lowering effects
title_short PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid‐lowering effects
title_sort pcsk9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: benefits beyond lipid‐lowering effects
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815840/
https://www.ncbi.nlm.nih.gov/pubmed/31557388
http://dx.doi.org/10.1111/jcmm.14586
work_keys_str_mv AT paleesiripong pcsk9inhibitorimprovescardiacfunctionandreducesinfarctsizeinratswithischaemiareperfusioninjurybenefitsbeyondlipidloweringeffects
AT mcsweeneychristianm pcsk9inhibitorimprovescardiacfunctionandreducesinfarctsizeinratswithischaemiareperfusioninjurybenefitsbeyondlipidloweringeffects
AT maneechotechayodom pcsk9inhibitorimprovescardiacfunctionandreducesinfarctsizeinratswithischaemiareperfusioninjurybenefitsbeyondlipidloweringeffects
AT moisescudalilam pcsk9inhibitorimprovescardiacfunctionandreducesinfarctsizeinratswithischaemiareperfusioninjurybenefitsbeyondlipidloweringeffects
AT jaiwongkamthidarat pcsk9inhibitorimprovescardiacfunctionandreducesinfarctsizeinratswithischaemiareperfusioninjurybenefitsbeyondlipidloweringeffects
AT kerdphoosasiwan pcsk9inhibitorimprovescardiacfunctionandreducesinfarctsizeinratswithischaemiareperfusioninjurybenefitsbeyondlipidloweringeffects
AT chattipakornsiripornc pcsk9inhibitorimprovescardiacfunctionandreducesinfarctsizeinratswithischaemiareperfusioninjurybenefitsbeyondlipidloweringeffects
AT chattipakornnipon pcsk9inhibitorimprovescardiacfunctionandreducesinfarctsizeinratswithischaemiareperfusioninjurybenefitsbeyondlipidloweringeffects