ミカミ　ヨシノリ   Mikami Yoshinori   三上　義礼    所属   東邦大学  医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Compensatory role of neuregulin-1 in diabetic cardiomyopathy
掲載誌名	正式名：Journal of Pharmacological Sciences 略　 称：J Pharmacol Sci ISSNコード：1347-8613/1347-8648
掲載区分	国外
出版社	Elsevier
巻・号・頁	153(3),pp.130-141
総ページ数	12
著者・共著者	Mikami Y†, Iwase F†, Ohshima D†, Tomida T†, Adachi-Akahane S＊†
担当区分	筆頭著者
発行年月	2023/09/01
概要	Diabetes mellitus is a prevalent risk factor for congestive heart failure. Diabetic cardiomyopathy patients present with left ventricular (LV) diastolic dysfunction at an early stage, then systolic dysfunction as the disease progresses. The mechanism underlying the development of diabetic cardiomyopathy has not yet been fully understood. This study aimed to elucidate the mechanisms by which diastolic dysfunction precedes systolic dysfunction at the early stage of diabetic cardiomyopathy. We hypothesized that the downregulation of cardioprotective factors is involved in the pathogenesis of diabetic cardiomyopathy. LV diastolic dysfunction, but not systolic dysfunction, was observed in type-1 diabetes mellitus model mice 4 weeks after STZ administration (STZ-4W), mimicking the early stage of diabetic cardiomyopathy. Counter to expectations, neuregulin-1 (NRG1) was markedly upregulated in the vascular endothelial cell in the ventricles of STZ-4W mice. To clarify the functional significance of the upregulated NRG1, we blocked its receptor ErbB2 with trastuzumab (TRZ). In STZ-4W mice, TRZ significantly reduced the systolic function without affecting diastolic function and caused a more prominent reduction in Akt phosphorylation levels. These results indicate that the compensatory upregulated NRG1 contributes to maintaining the LV systolic function, which explains why diastolic dysfunction precedes systolic dysfunction at the early stage of diabetic cardiomyopathy.
DOI	10.1016/j.jphs.2023.08.009
文献番号	37770154/PubMedID