附属病院 冠動脈集中治療部

木村 直行

キムラ ナオユキ  (NAOYUKI KIMURA)

基本情報

所属
自治医科大学 附属病院冠動脈集中治療部 教授
学位
医学博士(自治医科大学)

研究者番号
20382898
J-GLOBAL ID
201401043350806180
researchmap会員ID
B000238714

外部リンク

主要な経歴

 3

主要な論文

 135
  • Naoyuki Kimura, Masanori Nakamura, Reiya Takagi, Makiko Naka Mieno, Atsushi Yamaguchi, Martin Czerny, Friedhelm Beyersdorf, Fabian Alexander Kari, Bartosz Rylski
    Interactive cardiovascular and thoracic surgery 35(3) 2022年8月3日  
    OBJECTIVES: We aimed to determine whether non-A non-B aortic dissection (AD) differs in morphologic and haemodynamic properties from type B AD. METHODS: We simulated and compared haemodynamics of patients with acute type B or acute non-A non-B AD by means of computational fluid dynamics. Wall pressure and wall shear stress (WSS) in both the true lumen (TL) and false lumen (FL) at early, mid- and late systole were evaluated. Morphology, WSS and the FL/TL wall pressure ratio were compared between groups. RESULTS: Nineteen patients (type B, n = 7; non-A non-B, n = 12) were included. The median age (51 [46, 67] vs 53 [50, 63] years; P = 0.71) and a complicated course (14% vs 33%; P = 0.6) did not differ between the type B group and the non-A non-B group. However, the median entry tear width was increased in the non-A non-B group (9.7 [7.3, 12.7] vs 16.3 [11.9, 24.9] mm; P = 0.010). Streamlines showed, in patients with non-A non-B AD, blood from the TL flowed into the FL via the entry tear. Prevalence of a FL/TL wall pressure ratio >1.0 (type B versus non-A non-B) at early, mid- and late systole was 57% vs 83% (P = 0.31), 43% vs 83% (P = 0.13) and 57% vs 75% (P = 0.62), respectively. WSS did not differ between the groups. CONCLUSIONS: The increased FL/TL wall pressure ratio observed during systole in non-A non-B AD may beget a complicated presentation.
  • Denis R. Merk, Jocelyn T. Chin, Benjamin A. Dake, Lars Maegdefessel, Miquell O. Miller, Naoyuki Kimura, Philip S. Tsao, Cristiana Iosef, Gerald J. Berry, Friedrich W. Mohr, Joshua M. Spin, Cristina M. Alvira, Robert C. Robbins, Michael P. Fischbein
    CIRCULATION RESEARCH 110(2) 312-+ 2012年1月  査読有り
    Rationale: Marfan syndrome (MFS) is a systemic connective tissue disorder notable for the development of aortic root aneurysms and the subsequent life-threatening complications of aortic dissection and rupture. Underlying fibrillin-1 gene mutations cause increased transforming growth factor-beta (TGF-beta) signaling. Although TGF-beta blockade prevents aneurysms in MFS mouse models, the mechanisms through which excessive TGF-beta causes aneurysms remain ill-defined. Objective: We investigated the role of microRNA-29b (miR-29b) in aneurysm formation in MFS. Methods and Results: Using quantitative polymerase chain reaction, we discovered that miR-29b, a microRNA regulating apoptosis and extracellular matrix synthesis/deposition genes, is increased in the ascending aorta of Marfan (Fbn1(C1039G/+)) mice. Increased apoptosis, assessed by increased cleaved caspase-3 and caspase-9, enhanced caspase-3 activity, and decreased levels of the antiapoptotic proteins, Mcl-1 and Bcl-2, were found in the Fbn1(C1039G/+) aorta. Histological evidence of decreased and fragmented elastin was observed exclusively in the Fbn1(C1039G/+) ascending aorta in association with repressed elastin mRNA and increased matrix metalloproteinase-2 expression and activity, both targets of miR-29b. Evidence of decreased activation of nuclear factor kappa B, a repressor of miR-29b, and a factor suppressed by TGF-beta, was also observed in Fbn1(C1039G/+) aorta. Furthermore, administration of a nuclear factor kappa B inhibitor increased miR-29b levels, whereas TGF-beta blockade or losartan effectively decreased miR-29b levels in Fbn1(C1039G/+) mice. Finally, miR-29b blockade by locked nucleic acid antisense oligonucleotides prevented early aneurysm development, aortic wall apoptosis, and extracellular matrix deficiencies. Conclusions: We identify increased miR-29b expression as key to the pathogenesis of early aneurysm development in MFS by regulating aortic wall apoptosis and extracellular matrix abnormalities. (Circ Res. 2012;110:312-324.)

MISC

 33

共同研究・競争的資金等の研究課題

 16