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J Cardiovasc Dev Dis. 2019 Jun 4;6(2). pii: E22. doi: 10.3390/jcdd6020022.

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

Author information

1
Department of Biology Education, Faculty of Mathematics and Natural Science, Yogyakarta State University, Yogyakarta 55281, Indonesia. kartika.pertiwi@uny.ac.id.
2
Physiology and Pharmacology, College of Public, Medical and Veterinary Sciences, James Cook University, 4814 Townsville, Queensland, Australia. Rachael.kaye@my.jcu.edu.au.
3
Physiology and Pharmacology, College of Public, Medical and Veterinary Sciences, James Cook University, 4814 Townsville, Queensland, Australia. Coralie.scott@jcu.edu.au.
4
Physiology and Pharmacology, College of Public, Medical and Veterinary Sciences, James Cook University, 4814 Townsville, Queensland, Australia. lisa.chilton@jcu.edu.au.

Abstract

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.

KEYWORDS:

fibrosis; mitochondrial KATP channels; myofibroblasts; plasmalemmal KATP channels; α-smooth muscle actin

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