Time filter

Source Type

Qiao L.-N.,University of Sichuan | Wang X.-M.,Chengdu Women and Children Center Hospital | Liu Z.-Q.,University of Sichuan | Wang X.-Q.,University of Sichuan | And 3 more authors.
Journal of Sichuan University (Medical Science Edition) | Year: 2011

Objective: To explore the influence of inhibiting Notch signal on pulmonary vascular remodeling induced by PDGF. Methods: Vessel strips taken from healthy Wistar rats were cultured together with extrogenous PDGF, the potent smooth muscle cell proliferation stimulators, for 7 days. Some vessel strips were cultured with PDGF and γ-secretase inhibitor DAPT, a Notch signaling inhibitor for 7 days. Vascular wall thickness, PCNA and caspase-3 positive cell rate were examined in vessel strips. The alterations of Notch 1 to 4 receptor and HERP1, 2 mRNA were discerned by FQ-PCR to observe the influence of DAPT on Notch signal. At the same time, above indexes, which were related with pulmonary vascular remodeling, were measured too. Results PDGF stimulation in the cultured normal pulmonary arteries resulted in vascular medial thickness increase for about 50%, accompanied by significant increase in PCNA positive cell rate and decrease of caspase-3 positive cell rate. When DAPT were added to inhibit Notch signaling, the expression of HERP1, 2 mRNA decreased, the degrees of PDGF induced vascular medial thickness and PCNA positive cell rate increase as well as caspase-3 positive cell rate decrease were all attenuated notably. Conclusion Inhibiting Notch signal induced by γ-secretase inhibitor lead to the suppression of pulmonary vascular remodeling induced by PDGF, suggesting inhibition of Notch signal pathway might be a novel strategy in the intervention of pulmonary hypertension. Source

Qiao L.,University of Sichuan | Xie L.,University of Sichuan | Shi K.,Chengdu Women and Children Center Hospital | Zhou T.,University of Sichuan | And 2 more authors.
PLoS ONE | Year: 2012

Pulmonary hypertension (PH) is a fatal disease that lacks an effective therapy. Notch signaling pathway plays a crucial role in the angiogenesis and vascular remodeling. However, its roles in vascular remodeling in PH have not been well studied. In the current study, using hypoxia-induced PH model in rat, we examined the expression of Notch and its downstream factors. Then, we used vessel strip culture system and γ-secretase inhibitor DAPT, a Notch signaling inhibitor to determine the effect of Notch signaling in vascular remodeling and its potential therapeutic value. Our results indicated that Notch 1-4 were detected in the lung tissue with variable levels in different cell types such as smooth muscle cells and endothelial cells of pulmonary artery, bronchia, and alveoli. In addition, following the PH induction, all of Notch1, Notch3, Notch4 receptor, and downstream factor, HERP1 in pulmonary arteries, mRNA expressions were increased with a peak at 1-2 weeks. Furthermore, the vessel wall thickness from rats with hypoxia treatment increased after cultured for 8 days, which could be decreased approximately 30% by DAPT, accompanied with significant increase of expression level of apoptotic factors (caspase-3 and Bax) and transformation of vascular smooth muscle cell (VSMC) phenotype from synthetic towards contractile. In conclusion, the current study suggested Notch pathway plays an important role in pulmonary vascular remodeling in PH and targeting Notch signaling pathway could be a valuable approach to design new therapy for PH. © 2012 Qiao et al. Source

He M.L.,Chengdu Women and Children Center Hospital | Lai H.,Chengdu Women and Children Center Hospital | Cao Y.,Chengdu Women and Children Center Hospital | Shuai Y.Z.,Chengdu Women and Children Center Hospital | Yu S.C.,Chengdu Women and Children Center Hospital
Genetics and Molecular Research | Year: 2014

High resolution computed tomography (HRCT) was used to classify children with interstitial lung diseases (ILD). Sixty children with ILD underwent HRCT in supine position under free-respiratory conditions during scanning. Children under 5 years old were sedated with chloral hydrate and the scanning scope was from the lung apex to the diaphragm. In children older than 5 years old, scans were obtained at three levels: aortic arch, tracheal carina, and 1 cm above the right diaphragm. Five infectious patients were followed up. Two experienced radiologists read the films blindly to observe the type and distribution of ground-glass opacities and bronchovascular bundle abnormalities. Bronchovascular bundles were thick in 49 patients, and were thick and stiff in 27 patients. Of the 41 infectious patients, 39 showed thickened bronchovascular bundles, and 26 showed thick and stiff bronchovascular bundles. Of the 19 non-infectious patients, bronchovascular bundles were thickened in 10 patients, and were thick and stiff in 1 patient. Forty-one patients showed lobular ground-glass opacity (32 infectious, 9 non-infectious). Twenty-seven patients showed both bronchovascular bundle abnormality and lobular ground-glass opacity (20 infectious, 7 non-infectious). Eighteen patients showed patchy or mosaic ground-glass opacity (16 infectious, 2 non-infectious). There were 4 cases of bronchiectasis. HRCT is the first non-invasive diagnostic method for children with ILD, and its different manifestations can be classified. In early manifestation, bronchovascular bundles were abnormal and complicated with lobular ground-glass opacity. Patchy ground-glass opacity was the most common manifestation, and appeared to be difficult to disappear. Bronchiectasis indicated that the disease is irretrievable. © FUNPEC-RP. Source

Discover hidden collaborations