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Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of K(ATP) Channels
Ischemic preconditioning (IPC) and activation of ATP-sensitive potassium channels (K(ATP)) protect cardiac myocytes from ischemia reperfusion (IR) injury. We investigated the influence of IR injury, IPC and K(ATP) in isolated rat cardiac fibroblasts. Hearts were removed under isoflurane anesthesia....
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617075/ https://www.ncbi.nlm.nih.gov/pubmed/31167469 http://dx.doi.org/10.3390/jcdd6020022 |
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author | Pertiwi, Kartika R. Hillman, Rachael M. Scott, Coralie A. Chilton, Emily Lisa |
author_facet | Pertiwi, Kartika R. Hillman, Rachael M. Scott, Coralie A. Chilton, Emily Lisa |
author_sort | Pertiwi, Kartika R. |
collection | PubMed |
description | Ischemic preconditioning (IPC) and activation of ATP-sensitive potassium channels (K(ATP)) protect cardiac myocytes from ischemia reperfusion (IR) injury. We investigated the influence of IR injury, IPC and K(ATP) 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 K(ATP) with pinacidil (50 μM; 43 ± 6%) and by selectively opening mitochondrial K(ATP) (mK(ATP)) with diazoxide (100 μM; 53 ± 3%). Furthermore, IPC was attenuated by inhibiting K(ATP) with glibenclamide (10 μM; 23 ± 5%) and by selectively blocking mK(ATP) 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) K(ATP) were involved in IPC and (d) this protection involved selective activation of mK(ATP). |
format | Online Article Text |
id | pubmed-6617075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66170752019-07-18 Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of K(ATP) Channels Pertiwi, Kartika R. Hillman, Rachael M. Scott, Coralie A. Chilton, Emily Lisa J Cardiovasc Dev Dis Article Ischemic preconditioning (IPC) and activation of ATP-sensitive potassium channels (K(ATP)) protect cardiac myocytes from ischemia reperfusion (IR) injury. We investigated the influence of IR injury, IPC and K(ATP) 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 K(ATP) with pinacidil (50 μM; 43 ± 6%) and by selectively opening mitochondrial K(ATP) (mK(ATP)) with diazoxide (100 μM; 53 ± 3%). Furthermore, IPC was attenuated by inhibiting K(ATP) with glibenclamide (10 μM; 23 ± 5%) and by selectively blocking mK(ATP) 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) K(ATP) were involved in IPC and (d) this protection involved selective activation of mK(ATP). MDPI 2019-06-04 /pmc/articles/PMC6617075/ /pubmed/31167469 http://dx.doi.org/10.3390/jcdd6020022 Text en © 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pertiwi, Kartika R. Hillman, Rachael M. Scott, Coralie A. Chilton, Emily Lisa Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of K(ATP) Channels |
title | Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of K(ATP) Channels |
title_full | Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of K(ATP) Channels |
title_fullStr | Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of K(ATP) Channels |
title_full_unstemmed | Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of K(ATP) Channels |
title_short | Ischemia Reperfusion Injury Produces, and Ischemic Preconditioning Prevents, Rat Cardiac Fibroblast Differentiation: Role of K(ATP) Channels |
title_sort | ischemia reperfusion injury produces, and ischemic preconditioning prevents, rat cardiac fibroblast differentiation: role of k(atp) channels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617075/ https://www.ncbi.nlm.nih.gov/pubmed/31167469 http://dx.doi.org/10.3390/jcdd6020022 |
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