Altered expression of PPAR-γ and TRPC in neonatal rats with persistent pulmonary hypertension

Du, Yanna; Fu, Jianhua; Yao, Li; Lin, Qiao; Liu, Na; Xing, Yujiao; Xue, Xindong

doi:10.3892/mmr.2017.6744

Cited by 16 publications

(10 citation statements)

References 40 publications

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“…PPAR-γ is a member of the nuclear receptor hormone super family, and it is downregulated through TGF-β1 signaling in PASMC, whereas TRPC1 and 6 are upregulated in neonatal and adult rodents with hypoxic pulmonary hypertension. Conversely, stimulation of PPAR-γ reverses pulmonary hypertension and remodeling, and down regulates SOC expression ( Gong et al, 2011 ; Yang et al, 2015 ; Jiang et al, 2016 ; Du et al, 2017 ).…”

Section: Trp Stim Orai and Asic Proteins: Tension Development And mentioning

confidence: 99%

Revisiting the Role of TRP, Orai, and ASIC Channels in the Pulmonary Arterial Response to Hypoxia

et al. 2018

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The pulmonary arteries are exquisitely responsive to oxygen changes. They rapidly and proportionally contract as arterial PO2 decrease, and they relax as arterial PO2 is re-established. The hypoxic pulmonary vasoconstriction (HPV) is intrinsic since it does not require neural or endocrine factors, as evidenced in isolated vessels. On the other hand, pulmonary arteries also respond to sustained hypoxia with structural and functional remodeling, involving growth of smooth muscle medial layer and later recruitment of adventitial fibroblasts, secreted mitogens from endothelium and changes in the response to vasoconstrictor and vasodilator stimuli. Hypoxic pulmonary arterial vasoconstriction and remodeling are relevant biological responses both under physiological and pathological conditions, to explain matching between ventilation and perfusion, fetal to neonatal transition of pulmonary circulation and pulmonary artery over-constriction and thickening in pulmonary hypertension. Store operated channels (SOC) and receptor operated channels (ROC) are plasma membrane cationic channels that mediate calcium influx in response to depletion of internal calcium stores or receptor activation, respectively. They are involved in both HPV and pathological remodeling since their pharmacological blockade or genetic suppression of several of the Stim, Orai, TRP, or ASIC proteins in SOC or ROC complexes attenuate the calcium increase, the tension development, the pulmonary artery smooth muscle proliferation, and pulmonary arterial hypertension. In this Mini Review, we discussed the evidence obtained in in vivo animal models, at the level of isolated organ or cells of pulmonary arteries, and we identified and discussed the questions for future research needed to validate these signaling complexes as targets against pulmonary hypertension.

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Section: Trp Stim Orai and Asic Proteins: Tension Development And mentioning

confidence: 99%

Revisiting the Role of TRP, Orai, and ASIC Channels in the Pulmonary Arterial Response to Hypoxia

et al. 2018

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“…Researchers revealed that these expressions were observed in the cytoplasm of PASMCs and the expression of both proteins was greatly increased in the PAH group as compared with the rats in the CON group. [ 59 ] In the Western blot analysis performed in the same study, they also found that TRPC1 and TRPC6 protein expression was significantly increased as compared with the CON group. [ 59 ] HX selectively causes increased expression of TRPC1 and TRPC6 in mRNA and protein levels.…”

Section: Discussionmentioning

confidence: 92%

“…[ 59 ] In the Western blot analysis performed in the same study, they also found that TRPC1 and TRPC6 protein expression was significantly increased as compared with the CON group. [ 59 ] HX selectively causes increased expression of TRPC1 and TRPC6 in mRNA and protein levels. [ 60 ] Zhang et al [ 61 ] found significant increases in the level of mRNA in the hypoxic group in the PAH model that they created with chronic HX.…”

Section: Discussionmentioning

confidence: 95%

The effect of chloroquine on the TRPC1, TRPC6, and CaSR in the pulmonary artery smooth muscle cells in hypoxia‐induced experimental pulmonary artery hypertension

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et al. 2020

J Biochem & Molecular Tox

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Pulmonary arterial hypertension (PAH) is a life‐threatening disease characterized by a constant high pulmonary artery pressure and the remodeling of the vessel. Chloroquine (CLQ) has been observed to inhibit calcium influx. The aim of this study is to investigate the effect of CLQ on transient receptor cationic proteins (TRPC1 and TRPC6) and extracellular calcium‐sensitive receptor (CaSR) in a hypoxic PAH model. In this study, 8‐ to 12‐week‐old 32 male Wistar albino rats, weighing 200 to 300 g, were used. The rats were studied in four groups, including normoxy control, n = 8; normoxy CLQ (50 mg/kg/28 d), n = 8; hypoxia (HX; 10% oxygen/28 d) control, n = 8; and HX (10% oxygen/28 d) + CLQ (50 mg/kg), N = 8. Pulmonary arterial medial wall thickness, pulmonary arteriole wall, TRPC1, TRPC6, and CaSR expressions were evaluated by immunohistochemistry, polymerase chain reaction, and enzyme‐linked immunosorbent assay methods. At the end of the experiment, a statistically significant increase in the medial wall thickness was observed in the hypoxic group as compared with the control group. However, in the HX + CLQ group, there was a statistically significant decrease in the vessel medial wall as compared with the HX group. In the TRPC1‐, TRPC6‐, and CaSR‐immunopositive cell numbers, messenger RNA expressions and biochemical results showed an increase in the HX group, whereas they were decreased in the HX + CLQ group. The inhibitory effect of CLQ on calcium receptors in arterioles was observed in PAH.

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“…Berger et al (19) suggested that the BNP expression level in the plasma of patients with heart failure is significantly higher than that in the normal individuals, which is important for diagnosing and classifying heart failure. Du et al (20) also proposed that the BNP expression level in patients with PIH is significantly increased, with a diagnostic value. In the historical literature search, there are few studies on the correlation of miR-21 and BNP with PIH complicated with heart failure and their diagnostic values, which were detected and analyzed in the present study for clarification.…”

Section: Discussionmentioning

confidence: 99%

Correlation of miR-21 and BNP with pregnancy-inducedhypertension complicated with heart failureand the diagnostic value

et al. 2019

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Correlation of miR-21 and B-type natriuretic peptide (BNP) with pregnancy-induced hypertension (PIH) complicated with heart failure and the diagnostic value was investigated. Sixty patients with PIH complicated with heart failure admitted to Affiliated Hospital of Chengde Medical University from July 2016 to July 2017 were enrolled as the experimental group, and 35 normal pregnant women as the control group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method was used to determine the expression level of plasma miR-21 expression level. An automatic biochemical analyzer was used to determine plasma BNP expression level. Spearman's correlation analysis was used for the correlation analysis of miR-21 and BNP. ROC curve was used for evaluating the diagnostic values of miR-21 and BNP for PIH complicated with heart failure. miR-21 and BNP expression levels were higher in patients with PIH complicated with heart failure than those in the normal individuals, and were increased in line with the heart failure grade (P<0.001). The plasma miR-21 expression was positively correlated with BNP in patients with PIH complicated with heart failure (r=0.685, P<0.001). Both miR-21 and BNP had higher diagnostic values for PIH complicated with heart failure, in the diagnosis, the best cutoff value [odds ratio (OR)] of miR-21 was 1.113, with an area under curve (AUC) of 0.889 and a 95% confidence interval (CI) of 82.05-95.76%; the OR of BNP was 123, with an AUC of 0.747 and a 95% CI of 64.95-84.38%. Blood pressure, six-minute walk test (6MWT), left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were independent risk factors for the occurrence of PIH complicated with heart failure (P<0.05). In conclusion, miR-21 and BNP, highly expressed in patients with PIH complicated with heart failure, are expected to become important biomarkers for diagnosing PIH complicated with heart failure and judging the degree of heart failure in the patients, and worthy of clinical popularization and application.

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Altered expression of PPAR-γ and TRPC in neonatal rats with persistent pulmonary hypertension

Cited by 16 publications

References 40 publications

Revisiting the Role of TRP, Orai, and ASIC Channels in the Pulmonary Arterial Response to Hypoxia

Revisiting the Role of TRP, Orai, and ASIC Channels in the Pulmonary Arterial Response to Hypoxia

The effect of chloroquine on the TRPC1, TRPC6, and CaSR in the pulmonary artery smooth muscle cells in hypoxia‐induced experimental pulmonary artery hypertension

Correlation of miR-21 and BNP with pregnancy-inducedhypertension complicated with heart failureand the diagnostic value

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