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dc.contributor.authorSiripong Paleeen_US
dc.contributor.authorChristian M. McSweeneyen_US
dc.contributor.authorChayodom Maneechoteen_US
dc.contributor.authorDalila M. Moisescuen_US
dc.contributor.authorThidarat Jaiwongkamen_US
dc.contributor.authorSasiwan Kerdphooen_US
dc.contributor.authorSiriporn C. Chattipakornen_US
dc.contributor.authorNipon Chattipakornen_US
dc.description.abstract© 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.en_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titlePCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid-lowering effectsen_US
article.title.sourcetitleJournal of Cellular and Molecular Medicineen_US
article.volume23en_US of Manchesteren_US Mai Universityen_US
Appears in Collections:CMUL: Journal Articles

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