Dandan Zhang

Publications (3)10.31 Total impact

• Article: MicroRNA-138 plays a role in hypoxic pulmonary vascular remodeling by targeting Mst1.

  Shanshan Li, Yajuan Ran, Dandan Zhang, Jianguo Chen, Shuzhen Li, Daling Zhu
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  ABSTRACT: Unbalanced apoptosis is a major cause of structural remodeling of vasculatures associated with pulmonary arterial hypertension (PAH), while the underlying mechanisms are still elusive. MicroRNAs (miRNAs) regulate the expression of several proteins that are important for the cell fate including differentiation, proliferation and apoptosis. It is possible that these regulatory RNA molecules play a role in the development of PAH. To test this hypothesis, we studied the effect of several miRNAs on the apoptosis of cultured pulmonary artery smooth muscle cells (PASMCs), and identified miR-138 to be an important player. The miR-138 was expressed in PASMCs, and its expression is subject to hypoxia regulation. Expression of exogenous miR-138 suppressed PASMC apoptosis, prevented caspase activation, and disrupted the Bcl-2 signaling. The serine-threonine kinase (Mst1), an amplifier of cell apoptosis, seemed to be a target of miR-138, and the activation of the Akt pathway was necessary for the antiapoptotic effect of miR-138. Therefore, these results suggest that miR-138 appears to be a negative regulator of PASMC apoptosis, and play an important role in HPVR.
  Biochemical Journal 03/2013; · 4.90 Impact Factor
• Article: Osthole relaxes pulmonary arteries through endothelial Phosphatidylinositol 3-Kinase/Akt -eNOS -NO signaling pathway in rats.

  Li Yao, Ping Lu, Yumei Li, Lijing Yang, Hongxuan Feng, Yong Huang, Dandan Zhang, Jianguo Chen, Daling Zhu
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  ABSTRACT: Pulmonary arterial hypertension is a life-threatening disease lacking effective therapies. Osthole is a natural coumarin compound isolated from Angelica pubescens Maxim., which possesses hypotensive effect. Although its effects on isolated thoracic aorta (systemic circulating system) are clarified, it remains unclear whether Osthole relaxes isolated pulmonary arteries (PAs) (pulmonary circulating system). The aim of this study was to investigate the effects of Osthole on isolated PAs and the underlying mechanisms. We examined PA relaxation induced by Osthole in isolated human and rat PA rings with force-electricity transducers, the expression and activity of endothelial niric oxide synthase (eNOS) and protein kinase B (Akt) with western blot, and nitric oxide (NO) production using DAF-FM DA fluorescent indicator. The results showed that Osthole elicited a dose-dependent vasorelaxation activity with phenylephrine-precontracted human and rat PA rings, which can be diminished by endothelium denudation and inhibition of eNOS, while having no effect on rat mesenteric arteries. Osthole increased NO release as well as activation of Akt and eNOS, indicated with increased phosphorylations of Akt at Ser-473 and eNOS at Ser-1177 in endothelial cells. PI3K inhibitor LY294002 also blocked Osthole induced vasodilation. In summary, dilative effect of Osthole was dependent on endothelial integrity and NO production, and was mediated by endothelial PI3K/Akt-eNOS-NO pathway. These may provide a new pulmonary vasodilator for the therapy of pulmonary arterial hypertension.
  European journal of pharmacology 12/2012; · 2.59 Impact Factor
• Article: Effect of Mitofusin 2 on smooth muscle cells proliferation in hypoxic pulmonary hypertension.

  Dandan Zhang, Cui Ma, Shanshan Li, Yajuan Ran, Jianguo Chen, Ping Lu, Shuai Shi, Daling Zhu
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  ABSTRACT: Mitofusin 2 (Mfn2) is an important mitochondrial protein in maintaining mitochondrial network and bioenergetics. Recently, Mfn2 has been reported to have a potential role in regulating cell proliferation, apoptosis, and differentiation in many cell types. In this study, we performed immunohistochemistry, pulmonary artery smooth muscle cells (PASMCs) DNA analysis, proliferating cell nuclear antigen expression and cell cycle analysis to determine the role of Mfn2 in hypoxia-induced pulmonary vascular remodeling. Our results showed that hypoxia promoted the proliferation of pulmonary artery smooth muscle cells, including regulating more cells at G(2)/M+S phase, increasing proliferating cell nuclear antigen and Cyclin A expression, whereas all these effects of hypoxia were suppressed after the cells were treated with siRNA against Mfn2. Our results also proved that PI3K/Akt signaling pathway was involved in Mfn2-induced smooth muscle cell proliferation. Thus, these results indicate that Mfn2 mediates PASMC proliferation in hypoxic pulmonary hypertension via the PI3K/Akt signaling pathway.
  Microvascular Research 07/2012; · 2.83 Impact Factor