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MiR-15b-5p Regulates Collateral Artery Formation by Targeting AKT3 (Protein Kinase B-3).
Zhu, Ling-Ping; Zhou, Ji-Peng; Zhang, Jia-Xiong; Wang, Jun-Yao; Wang, Zhen-Yu; Pan, Miao; Li, Ling-Fang; Li, Chuan-Chang; Wang, Kang-Kai; Bai, Yong-Ping; Zhang, Guo-Gang.
Afiliação
  • Zhu LP; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
  • Zhou JP; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
  • Zhang JX; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
  • Wang JY; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
  • Wang ZY; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
  • Pan M; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
  • Li LF; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
  • Li CC; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
  • Wang KK; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
  • Bai YP; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
  • Zhang GG; From the Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China (L.-P.Z., J.-P.Z., J.-Y.W., Z.-Y.W., M.P., L.-F.L., L.C., G.-G.Z.); Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, China (J.-X.Z., C.-C.L., Y.-P.B.); a
Arterioscler Thromb Vasc Biol ; 37(5): 957-968, 2017 05.
Article em En | MEDLINE | ID: mdl-28254819
ABSTRACT

OBJECTIVE:

To identify circulating microRNAs that are differentially expressed in severe coronary heart disease with well or poorly developed collateral arteries and to investigate their mechanisms of action in vivo and in vitro. APPROACH AND

RESULTS:

In our study, we identified a circulating microRNA, miR-15b-5p, with low expression that, nevertheless, characterized patients with sufficient coronary collateral artery function. Moreover, in murine hindlimb ischemia model, in situ hybridization identified that miR-15b-5p was specifically expressed in vascular endothelial cells of adductors in sham group and was remarkably downregulated after femoral artery ligation. Overexpressed miR-15b-5p significantly inhibited arteriogenesis and angiogenesis in mice. In vitro, both under basal and vascular endothelial growth factor stimulation, loss-of-function or gain-of-function studies suggested that miR-15b-5p significantly promoted or depressed the migration and proliferation of endothelial cells. We identified AKT3 (protein kinase B-3) as a direct target of miR-15b-5p. Interestingly, AKT3 deficiency by injection with Chol-AKT3-siRNA obviously suppressed arteriogenesis and the recovery of blood perfusion after femoral ligation in mice.

CONCLUSIONS:

These results indicate that circulating miR-15b-5p is a suitable biomarker for discriminating between patients with well-developed or poorly developed collaterals. Moreover, miR-15b-5p is a key regulator of arteriogenesis and angiogenesis, which may represent a potential therapeutic target for ischemic disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença da Artéria Coronariana / Circulação Colateral / Músculo Esquelético / Circulação Coronária / Vasos Coronários / MicroRNAs / Proteínas Proto-Oncogênicas c-akt / Isquemia Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Arterioscler Thromb Vasc Biol Assunto da revista: ANGIOLOGIA Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença da Artéria Coronariana / Circulação Colateral / Músculo Esquelético / Circulação Coronária / Vasos Coronários / MicroRNAs / Proteínas Proto-Oncogênicas c-akt / Isquemia Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Arterioscler Thromb Vasc Biol Assunto da revista: ANGIOLOGIA Ano de publicação: 2017 Tipo de documento: Article