Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of KATP Channels

Pertiwi, Kartika R., Hillman, Rachael M., Scott, Coralie A., and Chilton, Lisa (2019) Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of KATP Channels. Journal of Cardiovascular Development and Disease, 6 (2). 22.

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Ischemic preconditioning (IPC) and activation of ATP-sensitive potassium channels (KATP) protect cardiac myocytes from ischemia reperfusion (IR) injury. We investigated the influence of IR injury, IPC and KATP in isolated rat cardiac fibroblasts. Hearts were removed under isoflurane anesthesia. IR was simulated in vitro by application and removal of paraffin oil over pelleted cells. Ischemia (30, 60 and 120 min) followed by 60 min reperfusion resulted in significant differentiation of fibroblasts into myofibroblasts in culture (mean % fibroblasts ± SEM in IR vs. time control: 12 ± 1% vs. 63 ± 2%, 30 min ischemia; 15 ± 3% vs. 71 ± 4%, 60 min ischemia; 8 ± 1% vs. 55 ± 2%, 120 min ischemia). IPC (15 min ischemia, 30 min reperfusion) significantly attenuated IR-induced fibroblast differentiation (52 ± 3%) compared to 60 min IR. IPC was mimicked by opening KATP with pinacidil (50 μM; 43 ± 6%) and by selectively opening mitochondrial KATP (mKATP) with diazoxide (100 μM; 53 ± 3%). Furthermore, IPC was attenuated by inhibiting KATP with glibenclamide (10 μM; 23 ± 5%) and by selectively blocking mKATP with 5-hydroxydecanoate (100 μM; 22 ± 9%). These results suggest that (a) IR injury evoked cardiac fibroblast to myofibroblast differentiation, (b) IPC attenuated IR-induced fibroblast differentiation, (c) KATP were involved in IPC and (d) this protection involved selective activation of mKATP.

Item ID: 65806
Item Type: Article (Research - C1)
ISSN: 2308-3425
Keywords: plasmalemmal KATP channels; mitochondrial KATP channels; myofibroblasts; α-smooth muscle actin; fibrosis
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Copyright Information: ©2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (
Funders: James Cook University (JCU)
Date Deposited: 04 Feb 2021 02:30
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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