Prolyl 4-Hydroxylase Domain Protein 3-Inhibited Smooth-Muscle-Cell Dedifferentiation Improves Cardiac Perivascular Fibrosis Induced by Obstructive Sleep Apnea.

Background. Intermittent hypoxia (IH) induced by obstructive sleep apnea (OSA) is a leading factor affecting cardiovascular fibrosis. Under IH condition, smooth muscle cells (SMAs) respond by dedifferentiation, which is associated with vascular remodelling. The expression of prolyl 4-hydroxylase dom...

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Publicado en:BioMed Research International pp. 1 - 13
Autores principales: Tong, Jiayi, Yu, Fu-chao, Li, Yang, Wei, Qin, Li, Chen, Zhen, Penghao, Zhang, Guanghao
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 6/27/2019
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 6/27/2019
      pid: 480
      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        137199427
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        10.1155/2019/9174218
        137199427
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        atl: Prolyl 4-Hydroxylase Domain Protein 3-Inhibited Smooth-Muscle-Cell Dedifferentiation Improves Cardiac Perivascular Fibrosis Induced by Obstructive Sleep Apnea.
      aug:
        au:
          Tong, Jiayi
          Yu, Fu-chao
          Li, Yang
          Wei, Qin
          Li, Chen
          Zhen, Penghao
          Zhang, Guanghao
        affil: Southeast University, China
      sug:
        subj:
          Oxidoreductases Pharmacodynamics
          Muscle, Smooth Drug Effects
          Cell Differentiation Drug Effects
          Cardiovascular System Physiology Drug Effects
          Sleep Apnea, Obstructive Complications
          Fibrosis Etiology
          Cardiovascular Diseases Etiology
          Animal Studies
          Mice
          Anoxia
          In Vivo Studies
          In Vitro Studies
          Gene Expression
          Collagen
          Transcription Factors Drug Effects
      ab: Background. Intermittent hypoxia (IH) induced by obstructive sleep apnea (OSA) is a leading factor affecting cardiovascular fibrosis. Under IH condition, smooth muscle cells (SMAs) respond by dedifferentiation, which is associated with vascular remodelling. The expression of prolyl 4-hydroxylase domain protein 3 (PHD3) increases under hypoxia. However, the role of PHD3 in OSA-induced SMA dedifferentiation and cardiovascular fibrosis remains uncertain. Methods. We explored the mechanism of cardiovascular remodelling in C57BL/6 mice exposed to IH for 3 months and investigated the mechanism of PHD3 in improving the remodelling in vivo and vitro. Results. In vivo remodelling showed that IH induced cardiovascular fibrosis via SMC dedifferentiation and that fibrosis improved when PHD3 was overexpressed. In vitro remodelling showed that IH induced SMA dedifferentiation, which secretes much collagen I. PHD3 overexpression in cultured SMCs reversed the dedifferentiation by degrading and inactivating HIF-1α. Conclusion. OSA-induced cardiovascular fibrosis was associated with SMC dedifferentiation, and PHD3 overexpression may benefit its prevention by reversing the dedifferentiation. Therefore, PHD3 overexpression has therapeutic potential in disease treatment.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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