α1-Adrenergic receptor mediates adipose-derived stem cell sheet-induced protection against chronic heart failure after myocardial infarction in rats.

Autor: Horie H; Division of Cardiovascular Surgery, Department of Surgery, Tottori University Faculty of Medicine, Yonago, Japan., Hisatome I; Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan., Kurata Y; Department of Physiology II, Kanazawa Medical University, Uchinada, Japan. yasu@kanazawa-med.ac.jp., Yamamoto Y; Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan., Notsu T; Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan., Adachi M; Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan., Li P; Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan., Kuwabara M; Intensive Care Unit and Department of Cardiology, Toranomon Hospital, Tokyo, Japan., Sakaguchi T; Division of Medical Education, Department of Medical Education, Tottori University Faculty of Medicine, Yonago, Japan., Kinugasa Y; Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Yonago, Japan., Miake J; Department of Pharmacology, Tottori University Faculty of Medicine, Yonago, Japan., Koba S; Division of Integrative Physiology, Faculty of Medicine, Tottori University, Yonago, Japan., Tsuneto M; Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan., Shirayoshi Y; Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science, Yonago, Japan., Ninomiya H; Department of Biological Regulation, Tottori University Faculty of Medicine, Yonago, Japan., Ito S; Department of Clinical Research and Development, National Cerebral and Cardiovascular Center, Suita, Japan., Kitakaze M; Hanwa Daini Senboku Hospital, Sakai, Osaka, Japan., Yamamoto K; Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Yonago, Japan., Yoshikawa Y; Division of Cardiovascular Surgery, Department of Surgery, Tottori University Faculty of Medicine, Yonago, Japan., Nishimura M; Division of Cardiovascular Surgery, Department of Surgery, Tottori University Faculty of Medicine, Yonago, Japan.
Jazyk: angličtina
Zdroj: Hypertension research : official journal of the Japanese Society of Hypertension [Hypertens Res] 2022 Feb; Vol. 45 (2), pp. 283-291. Date of Electronic Publication: 2021 Dec 01.
DOI: 10.1038/s41440-021-00802-2
Abstrakt: Cell-based therapy using adipose-derived stem cells (ADSCs) has emerged as a novel therapeutic approach to treat heart failure after myocardial infarction (MI). The purpose of this study was to determine whether inhibition of α1-adrenergic receptors (α1-ARs) in ADSCs attenuates ADSC sheet-induced improvements in cardiac functions and inhibition of remodeling after MI. ADSCs were isolated from fat tissues of Lewis rats. In in vitro studies using cultured ADSCs, we determined the mRNA levels of vascular endothelial growth factor (VEGF)-A and α1-AR under normoxia or hypoxia and the effects of norepinephrine and an α1-blocker, doxazosin, on the mRNA levels of angiogenic factors. Hypoxia increased α1-AR and VEGF mRNA levels in ADSCs. Norepinephrine further increased VEGF mRNA expression under hypoxia; this effect was abolished by doxazosin. Tube formation of human umbilical vein endothelial cells was promoted by conditioned media of ADSCs treated with the α1 stimulant phenylephrine under hypoxia but not by those of ADSCs pretreated with phenylephrine plus doxazosin. In in vivo studies using rats with MI, transplanted ADSC sheets improved cardiac functions, facilitated neovascularization, and suppressed fibrosis after MI. These effects were abolished by doxazosin treatment. Pathway analysis from RNA sequencing data predicted significant upregulation of α1-AR mRNA expression in transplanted ADSC sheets and the involvement of α1-ARs in angiogenesis through VEGF. In conclusion, doxazosin abolished the beneficial effects of ADSC sheets on rat MI hearts as well as the enhancing effect of norepinephrine on VEGF expression in ADSCs, indicating that ADSC sheets promote angiogenesis and prevent cardiac dysfunction and remodeling after MI via their α1-ARs.
(© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)
Databáze: MEDLINE
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