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

© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. During acute cardiac ischaemia/reperfusion (I/R), an increased plasma proprotein convertase subtilisin/kexin 9 (PCSK9) level instigates inflamma...

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Main Authors: Siripong Palee, Christian M. McSweeney, Chayodom Maneechote, Dalila M. Moisescu, Thidarat Jaiwongkam, Sasiwan Kerdphoo, Siriporn C. Chattipakorn, Nipon Chattipakorn
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Published: 2020
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/67606
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spelling th-cmuir.6653943832-676062020-04-02T14:56:33Z PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid-lowering effects Siripong Palee Christian M. McSweeney Chayodom Maneechote Dalila M. Moisescu Thidarat Jaiwongkam Sasiwan Kerdphoo Siriporn C. Chattipakorn Nipon Chattipakorn Biochemistry, Genetics and Molecular Biology © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. 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. 2020-04-02T14:56:33Z 2020-04-02T14:56:33Z 2019-11-01 Journal 15821838 2-s2.0-85073919672 10.1111/jcmm.14586 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85073919672&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/67606
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Biochemistry, Genetics and Molecular Biology
spellingShingle Biochemistry, Genetics and Molecular Biology
Siripong Palee
Christian M. McSweeney
Chayodom Maneechote
Dalila M. Moisescu
Thidarat Jaiwongkam
Sasiwan Kerdphoo
Siriporn C. Chattipakorn
Nipon Chattipakorn
PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid-lowering effects
description © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. 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 Journal
author Siripong Palee
Christian M. McSweeney
Chayodom Maneechote
Dalila M. Moisescu
Thidarat Jaiwongkam
Sasiwan Kerdphoo
Siriporn C. Chattipakorn
Nipon Chattipakorn
author_facet Siripong Palee
Christian M. McSweeney
Chayodom Maneechote
Dalila M. Moisescu
Thidarat Jaiwongkam
Sasiwan Kerdphoo
Siriporn C. Chattipakorn
Nipon Chattipakorn
author_sort Siripong Palee
title 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_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_sort pcsk9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: benefits beyond lipid-lowering effects
publishDate 2020
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85073919672&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/67606
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