ウサギモデルにおけるマイクロRNA-126含有ナノ粒子を積層したステントによる新生内膜形成の抑制効果の検討

京都大学0048新制・課程博士博士(医学)甲第20797号医博第4297号新制||医||1025(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 湊谷 謙司, 教授 齊藤 博英, 教授 Shohab YOUSSEFIAN学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

On a nonlocal system for vegetation in drylands

International audienceSeveral mathematical models are proposed to understand spatial patchy vegetation patterns arising in drylands. In this paper, we consider the system with nonlocal dispersal of plants (through a redistribution kernel for seeds) proposed by Pueyo et al. (Oikos 117:1522-1532, 2008) as a model for vegetation in water-limited ecosystems. It consists in two reaction diffusion equations for surface water and soil water, combined with an integro-differential equation for plants. For this system, under suitable assumptions, we prove well-posedness using the Schauder fixed point theorem. In addition, we consider the stationary problem from the viewpoint of vegetated pattern formation, and show a transition of vegetation patterns when parameter values (rainfall, seed dispersal range, seed germination rate) in the system vary. The influence of the shape of the redistribution kernel is also discussed

High-density lipoprotein cholesterol levels and cardiovascular outcomes in Japanese patients after percutaneous coronary intervention: a report from the CREDO-Kyoto registry cohort-2.

[Objective]To determine whether low HDL-C is a risk factor for adverse cardiovascular events in patients with known CAD. [Methods]We evaluated 10, 391 patients who underwent PCI from January 2005 to December 2007. In total, 3838 (36.9%) patients had low HDL-C (HDL-C <40 mg/dL in males and <50 mg/dL in females) and 6553 (63.1%) patients had normal HDL-C based on measurements on admission. [Results]The unadjusted 5-year incidence of major adverse cardiac events (MACE: composite of cardiovascular death, myocardial infarction or stroke) was significantly higher in the low HDL-C group than in the normal HDL-C group (17.6% vs. 14.0%, P < 0.0001). However, after adjusting for confounders, low HDL-C was not associated with a higher risk of MACE (adjusted hazard ratio [HR] 1.07, 95% confidence interval (CI) 0.97?1.19; P = 0.19). There was no significant interaction between the effect of low HDL-C on MACE and several subgroup factors including age, sex, clinical presentation of CAD, statins use, serum low-density lipoprotein cholesterol level, and serum triglycerides level. [Conclusion]Low HDL-C, as compared with normal HDL-C, was not associated with higher 5-year risk of MACE in patients who underwent PCI

Expression patterns of miRNA-423-5p in the serum and pericardial fluid in patients undergoing cardiac surgery

Background: Recently, it has been reported that specific microRNA (miRNA) levels are elevated in serum and can be used as biomarkers in patients with cardiovascular diseases. However, miRNAs expression profiles and their sources in pericardial fluid (PF) are unclear. Methods and Results: The purpose of this study was to identify the levels of miRNAs in PF in relation to those in the serum in patients undergoing cardiac surgery. Serum (S) and PF from patients undergoing coronary artery bypass graft (CABG) due to stable angina pectoris (sAP) and unstable AP (uAP) and aortic valve replacement due to aortic stenosis (AS) were analyzed for the detection of miRNAs. We named these samples S-sAP, S-uAP, S-AS, PF-sAP, PF-uAP, and PF-AS, respectively. We first measured the levels of miR-423-5p, which was recognized previously as a biomarker for heart failure. miR-423-5p levels were significantly higher in PF than serum. Although there was no difference in miR-423-5p levels among the PF-AS, PF-sAP, and PF-uAP, its levels were significantly elevated in S-uAP compared with those in S-AS and S-sAP. In order to clarify the source of miR-423-5p in PF, we measured the levels of muscle-enriched miR-133a and vascular-enriched miR-126 and miR-92a in the same samples. miR-133a levels were significantly higher in serum than in PF, and it was elevated in S-uAP compared with S-AS. miR-126 level was significantly increased in serum compared with PF, and the level of miR-92a the similar tendency. miR-423-5p is located in the first intron of NSRP1. There is another miRNA, miR-3184, encoded in the opposite direction in the same region. In vitro experiments indicated that the duplex of miR-423-5p and miR-3184-3p was more resistant to RNase than the duplex of miR-423-5p and miR-133-3p, which may help to stabilize miR-423-5p in the PF. Conclusions: Our results suggested that miR-423-5p is enriched in PF, and serum miR-423-5p may be associate with uAP. Its expression pattern was different to that of muscle- and vascular-enriched miRNAs, miR-133a, miR-126, and miR-92a

MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice

脂肪酸とコレステロール合成の切り替えスイッチの発見に成功 -安全な動脈硬化改善薬の開発に期待-. 京都大学プレスリリース. 2013-12-03.MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports have indicated that miR-33, which is located within the intron of sterol regulatory element-binding protein (SREBP) 2, controls cholesterol homoeostasis and may be a potential therapeutic target for the treatment of atherosclerosis. Here we show that deletion of miR-33 results in marked worsening of high-fat diet-induced obesity and liver steatosis. Using miR-33−/−Srebf1+/− mice, we demonstrate that SREBP-1 is a target of miR-33 and that the mechanisms leading to obesity and liver steatosis in miR-33−/− mice involve enhanced expression of SREBP-1. These results elucidate a novel interaction between SREBP-1 and SREBP-2 mediated by miR-33 in vivo

MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo.

マウスへのマイクロRNA-33bの導入に成功 -ヒトでのHDL-コレステロールの質の改善に期待-. 京都大学プレスリリース. 2014-06-17.MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports, including ours, indicated that miR-33a located within the intron of sterol regulatory element-binding protein (SREBP) 2 controls cholesterol homeostasis and can be a possible therapeutic target for treating atherosclerosis. Primates, but not rodents, express miR-33b from an intron of SREBF1. Therefore, humanized mice, in which a miR-33b transgene is inserted within a Srebf1 intron, are required to address its function in vivo. We successfully established miR-33b knock-in (KI) mice and found that protein levels of known miR-33a target genes, such as ABCA1, ABCG1, and SREBP-1, were reduced compared with those in wild-type mice. As a consequence, macrophages from the miR-33b KI mice had a reduced cholesterol efflux capacity via apoA-I and HDL-C. Moreover, HDL-C levels were reduced by almost 35% even in miR-33b KI hetero mice compared with the control mice. These results indicate that miR-33b may account for lower HDL-C levels in humans than those in mice and that miR-33b is possibly utilized for a feedback mechanism to regulate its host gene SREBF1. Our mice will also aid in elucidating the roles of miR-33a/b in different genetic disease models