PMID- 29573957 OWN - NLM STAT- MEDLINE DCOM- 20181016 LR - 20181016 IS - 1444-2892 (Electronic) IS - 1443-9506 (Linking) VI - 27 IP - 8 DP - 2018 Aug TI - Vitamin D Improves Cardiac Function After Myocardial Infarction Through Modulation of Resident Cardiac Progenitor Cells. PG - 967-975 LID - S1443-9506(18)30037-4 [pii] LID - 10.1016/j.hlc.2018.01.006 [doi] AB - BACKGROUND: Vitamin D has been implicated in the prevention of heart failure. However the underlying mechanism remains unclear. We hypothesised that these effects may be partially mediated by cardiac stem/progenitor cells (CPCs). Therefore, we examined the effects of 1,25-dihydroxyvitamin D3 (1,25D) on cell cycle activity and differentiation of a previously described CPC population called cardiac colony-forming unit fibroblasts (cCFU-Fs). METHODS: cCFU-Fs were isolated from adult male C57Bl/6 mouse hearts using fluorescence-activated cell sorting. The effect of 1,25D on cell proliferation and differentiation were was assessed by colony-forming and fibroblast differentiation assays. Cell cycle was analysed by flow cytometry. Mice with induced myocardial infarction (MI) were treated with 1,25D or vehicle controls and cardiac function assessed by echocardiography. RESULTS: 1,25D dose-dependently increased expression of vitamin D receptor (Vdr) and reduced large colony formation. Addition of 1,25D to cCFU-Fs slowed cell proliferation, promoted cell cycle arrest and decreased expression of pro-fibrotic factors during TGF-beta-induced fibroblast differentiation of cCFU-Fs. After MI, 1,25D-treated mice had less left ventricular wall thinning and significant improvement in left ventricular systolic function compared to vehicle-treated controls. Although no significant changes in myocardial fibrotic area and cardiomyocyte size were noted, treatment with 1,25D significantly inhibited cardiac interstitial cell proliferation after MI. CONCLUSIONS: Vitamin D signalling promotes cardioprotection after myocardial infarction. This may be through modulation of cCFU-F cell cycle. The role of 1,25D and VDR in regulating cardiac stem/progenitor cell function therefore warrants further investigation. CI - Copyright (c) 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved. FAU - Le, Thi Y L AU - Le TYL AD - Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia. FAU - Ogawa, Masahito AU - Ogawa M AD - Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia; Victor Chang Cardiac Research Institute, Sydney, NSW, Australia. FAU - Kizana, Eddy AU - Kizana E AD - Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. FAU - Gunton, Jenny E AU - Gunton JE AD - Centre for Diabetes, Obesity and Endocrinology, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. FAU - Chong, James J H AU - Chong JJH AD - Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Westmead Hospital, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Victor Chang Cardiac Research Institute, Sydney, NSW, Australia. Electronic address: james.chong@sydney.edu.au. LA - eng PT - Journal Article DEP - 20180203 PL - Australia TA - Heart Lung Circ JT - Heart, lung & circulation JID - 100963739 RN - 0 (Vitamins) RN - 1406-16-2 (Vitamin D) SB - IM MH - Animals MH - Cell- and Tissue-Based Therapy/*methods MH - Cells, Cultured MH - Disease Models, Animal MH - Echocardiography MH - Flow Cytometry MH - Heart Failure/etiology/*prevention & control MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Myocardial Infarction/diagnosis/*therapy MH - Myocytes, Cardiac/*cytology MH - Stem Cells/*cytology MH - Vitamin D/*therapeutic use MH - Vitamins/therapeutic use OTO - NOTNLM OT - Cardiac progenitor cells OT - Heart failure OT - Myocardial infarction OT - Myocardial protection OT - Vitamin D EDAT- 2018/03/27 06:00 MHDA- 2018/10/17 06:00 CRDT- 2018/03/26 06:00 PHST- 2017/09/20 00:00 [received] PHST- 2017/12/04 00:00 [revised] PHST- 2018/01/04 00:00 [accepted] PHST- 2018/03/27 06:00 [pubmed] PHST- 2018/10/17 06:00 [medline] PHST- 2018/03/26 06:00 [entrez] AID - S1443-9506(18)30037-4 [pii] AID - 10.1016/j.hlc.2018.01.006 [doi] PST - ppublish SO - Heart Lung Circ. 2018 Aug;27(8):967-975. doi: 10.1016/j.hlc.2018.01.006. Epub 2018 Feb 3.