PCSK9 inhibitor improves cardiac function and reduces infarct size in rats with ischaemia/reperfusion injury: Benefits beyond lipid‐lowering effects
| Autor: | Chayodom Maneechote, Sasiwan Kerdphoo, Siriporn C. Chattipakorn, Thidarat Jaiwongkam, Siripong Palee, Christian M. McSweeney, Nipon Chattipakorn, Dalila M. Moisescu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cardiac function curve Male medicine.medical_specialty Cardiotonic Agents PCSK9 inhibitor Ischemia Myocardial Ischemia Myocardial Reperfusion Injury heart Mitochondrion 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals cardiovascular diseases Rats Wistar Cardioprotection business.industry PCSK9 PCSK9 Inhibitors Cardiac arrhythmia Arrhythmias Cardiac Cell Biology Original Articles medicine.disease reperfusion injury Lipids Rats mitochondria 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Cardiology cardiovascular system Molecular Medicine Original Article ischaemia business Reperfusion injury |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text