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Anesthetic preconditioning in human cardiomyocytes derived from non‐diabetic and diabetic‐induced pluripotent stem cells
Author(s) -
Canfield Scott Glen,
Sepac Ana,
Sedlic Filip,
Muravyeva Maria,
Park Frank,
Bosnjak Zeljko
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1043.9
Subject(s) - induced pluripotent stem cell , anesthetic , diabetes mellitus , medicine , human induced pluripotent stem cells , anesthesia , chemistry , endocrinology , embryonic stem cell , biochemistry , gene
Diabetes and hyperglycemia have shown to attenuate the cardioprotective effects of anesthetic pre‐conditioning (APC) from an ischemic injury. We have developed an experimental in vitro model based on differentiation of human cardiomyocytes (CMs) from induced pluripotent stem cells (iPSCs) to further investigate the effects of genetic background and environmental factors on the attenuation of APC in diabetic individuals. CMs were generated by the differentiation of non‐diabetic and type II diabetic‐induced pluripotent stem cells; N‐iPSC and DM‐iPSC, respectively. The presence of 25 mM glucose alone inhibited mitoK ATP opening and expedited the opening of mitochondrial permeability transition pore (mPTP), resulting in an attenuation of APC cardioprotection. In DM‐CMs there was a reduction in mitoK ATP opening in response to isoflurane compared to N‐CMs. In N‐CMs, APC delayed mPTP opening; however, in DM‐CMs, APC was ineffective in delaying mPTP opening. Cardiomyocytes from N‐iPSCs and DM‐iPSCs enables comparative studies addressing genetic and environmental mechanisms. Preliminary results indicate that both a diabetic background and a high glucose environment have detrimental effects on mPTP opening and the actions of isoflurane to induce mitoK ATP opening as a possible explanation for the inefficiency of APC. Supported by P01GM066730 and R01HL034708 (ZJB) from the NIH, Bethesda, MD.