Objective To investigative the effects of combination treatment with simvastatin and aspirin in a rat model of monocrotaline-induced pulmonary hypertension. Methods Sixty male Sprague-Dawley rats were randomly divided into a control group, a simvastatin group, an aspirin group, and a combination treatment group. The control group received monocrotaline injection subcutaneously to induce pulmonary hypertension. Simvastatin ( 2 mg/kg) , aspirin ( 1 mg/kg) , or simvastatin ( 2 mg/kg) + aspirin ( 1 mg/kg) was administered once daily to the rats of treatment groups respectively for 28 days after monocrotaline injection. Mean pulmonary arterial pressure ( mPAP) was detected by right heart catheter.Right ventricular hypertrophy index ( RVHI) was calculated as the right ventricle to the left ventricle plus septum weight. Histopathology changes of small intrapulmonary arteries were evaluated via image analysissystem. Interleukin-6 ( IL-6) level in lung tissue was determined by ELISA.Results Compared with the control group, simvastatin or aspirin decreased mPAP [ ( 34. 1 ±8. 4) mm Hg, ( 38. 3 ±7. 1) mmHg vs.( 48. 4 ±7. 8) mmHg] and increased arterial wall diameter significantly ( P lt; 0. 05) . The combination treatment group showed more significant improvement in mPAP, RVHI and pulmonary arterial remodeling compared with each monotherapy ( P lt;0. 05) . Moreover, the combination therapy had additive effects on the increases in lung IL-6 levels and the perivascular inflammation score. Conclusions Combination therapy with simvastatin and aspirin is superior in preventing the development of pulmonary hypertension. The additive effect of combination therapy is suggested to be ascribed to anti-inflammation effects.
Objective To investigate the effects of simvastatin on monocrotaline-induced pulmonary hypertension in rats, and explore the potential mechanism of simvastatin by blocking heme oxygenase-1( HO-1) expression. Methods 52 male Sprague-Dawley rats were randomly divided into five groups, ie. a control group, a simvastatin control group, a pulmonary hypertension model group, a simvastatin treatment group, a ZnPP ( chemical inhibitor of HO) group. Mean pulmonary arterial pressure ( mPAP) and right ventricular systolic pressure ( RVSP) were detected by right heart catheter at 5th week. Right ventricular hypertrophy index ( RVHI) was calculated as the right ventricle to the left ventricle plus septum weight. Histopathology changes of small intrapulmonary arteries were evaluated via image analysis system.Immunohistochemical analysis was used to investigate the expression and location of HO-1. HO-1 protein level in lung tissue were determined by western blot. Results Compared with the model group, simvastatin treatment decreased mPAP and RVHI significantly [ ( 35. 63 ±5. 10) mm Hg vs. ( 65. 78 ±15. 51) mm Hg,0. 33 ±0. 05 vs. 0. 53 ±0. 06, both P lt; 0. 05 ] . Moreover, simvastatin treatment partially reversed the increase of arterial wall area and arterial wall diameter [ ( 50. 78 ±9. 03 ) % vs. ( 65. 92 ±7. 19) % ,( 43. 75 ±4. 23) % vs. ( 52. 00 ±5. 35) % , both P lt; 0. 01) . In the model group, HO-1 staining was primarily detected in alveolar macrophages. Simvastatin treatment increased HO-1 protein expression significantly, especially in the thickened smooth muscle layer and alveolar macrophages. Inhibiting HO-1 expression using ZnPP resulted in a loss of the effects of simvastatin. mPAP in the ZnPP group was ( 52. 88±17. 45) mm Hg, while arterial wall area and arterial wall diameter were ( 50. 78 ±9. 03) % and ( 52. 00 ±5. 35) % , respectively. Conclusions Simvastatin attenuates established pulmonary arterial hypertension andpulmonary artery remodeling in monocrotaline-induced pulmonary hypertension rats. The effect of simvastatin is associated with HO-1.
Objective To systematically review whether the prevalence of left ventricular diastolic dysfunction was higher in systemic sclerosis (SSc) patients. Methods The Cochrane Library, PubMed, EMbase, CBM, CNKI and WanFang Data databases were electronically searched to collect the studies about comparing echocardiographic parameters in SSc patients and controls from January 1990 to June 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software. Results A total of 22 studies involving 1 146 patients were included. The results of meta-analysis showed that: compared to controls, patients with SSc had prolonged left isovolumetric relaxation time (MD=10.40, 95%CI 4.04 to 16.77, P=0.001), higher trans-mitral A-wave velocity (MD=0.11, 95%CI 0.07 to 0.15, P<0.000 01), prolonged mitral deceleration time (MD=8.04, 95%CI 2.66 to 13.42,P=0.003), larger mean left atrial dimension (MD=1.43, 95%CI 0.11 to 2.76, P=0.03), higher estimated pulmonary artery pressure (MD=11.35, 95%CI 6.08 to 16.6, P<0.001), higher E/E’ ratio (MD=2.08, 95%CI 0.19 to 3.96,P=0.03) and lower trans-mitral E-wave velocity (MD=–0.03, 95%CI –0.05 to –0.01, P=0.000 3), mitral E/A ratio (MD=–0.24, 95%CI –0.32 to –0.15, P<0.000 01) and trans-mitral E’-wave velocity (MD=–1.52, 95%CI –2.44 to –0.60,P=0.001). There were no differences in left ventricular ejection fraction, isovolumetric end-systolic dimension, septal end-diastolic thickness and posterior wall end-diastolic thickness, trans-mitral A’-wave velocity, E’/A’ ratio. Conclusion SSc patients are more likely to have echocardiographic parameters of LVDD. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.
Objective To summarize the clinical features of motor neuron disease ( MND) with main presentation of pulmonary hypertension, so as to improve the diagnosis.Methods A patientwithMND whose main presentation was pulmonary hypertension was analyzed retrospectively. Meanwhile related literatures were reviewed. Clinical data including symptoms, early signs, misdiagnosis causes, and necessary functional examination of respiratory muscle were collected. Results The symptoms of MND was slow-onset and insidious with gradual progression over time. History inquiring found that the symptoms of muscle wasting and physical debilitation emerged long time before the respiratory symptoms. Physical examination also revealed obvious sign of muscle atrophy. Conclusions MND with main presentation of pulmonary hypertension has been recognized insufficiently and often misdiagnosed as other pulmonary diseases. Detailed history taking, systematic physical examination, and convenient functional examination of respiratory muscle,can not only reduce misdiagnosis, but also avoid some expensive and traumatic process.
Objective To investigate the dynamic expression of small ubiquitin-related modifiers-1 ( SUMO-1) in lung tissue in different phases of rat model of hypoxic pulmonary hypertension( HPH) .Methods Forty Wistar rats were randomly divided into 5 groups, and exposed to normoxia or to normobaric intermittent hypoxia for 3, 7, 14 or 21 days, respectively. Mean pulmonary arterial pressure( mPAP) , right ventricle hypertrophy index ( RVHI) , and the ratio of the vessel wall area to the total area( WA% ) weremeasured. RT-PCR and in situ hybridization were used to determine the mRNA expression of SUMO-1.Immunohistochemistry and Western blot were used to determine the protein expression of SUMO-1. Results The hypoxic rats developed pulmonary vascular remodeling in pulmonary arterioles after 7 days of hypoxia,with WA% and mPAP significantly higher than those in the normal control. Pulmonary vascular remodeling aggravated with much higherWA% and mPAP afer 14 days of hypoxia, and reached the peak afer 21 days of hypoxia. SUMO-1 mRNA and protein expression markedly increased after 3 days of hypoxia, and reached peak after 14 days. After 21 days of hypoxia, SUMO-1 mRNA expression weakened but still higher than that in the normal control ( P lt; 0. 05) , and SUMO-1 protein expression remained stable. SUMO-1 mRNA and protein expression were positively correlated with mPAP, WA% and RVHI( all P lt; 0. 01) . Conclusion SUMO-1 is transcriptionally induced in lung tissue under chronic hypoxia, and thus involves in the pathogenesis of HPH.
ObjectiveBased on real-word data, and compared with two common chronic respiratory diseases, interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), this case-control study plans to investigate the risk factors and clinical characteristics of patients with combined pulmonary fibrosis and emphysema syndrome (CPFE).MethodsA retrospective case-control study was carried out to screen the clinical data of 96 patients with CPFE, 133 patients with COPD and 164 patients with ILD, analyze their demographics, clinical data, complications and related clinical indicators. Univariate analysis was used to compare the differences among the three groups, and multivariate logistic analysis was used to screen for risk factors.ResultsAll three groups were in old age with the average age of above 71 years. In terms of male ratio and smoking rate, the CPFE group (93.8%, 85.4%) was higher than the ILD group (75.0%, 64.0%), but there was no significant difference when compared with the COPD group (90.2%, 82.0%). Regarding comorbid disease, the proportion of connective tissue disease (CTD) in the CPFE group (10.4%) and the ILD group (13.4%) was higher than that in the COPD group (1.5%). The proportion of hyperlipidemia in the CPFE group (8.3%) was higher than that in the COPD group (1.5%) and the ILD group (1.2%). There were differences in the abnormal proportion of antinuclear antibody among the three groups, but no significant difference was found when compared with the CPFE group alone. The CPFE group (46.9%, 12.5%) and the ILD group (54.9%, 9.8%) were significantly higher than the COPD group (34.6%, 2.3%) in terms of carcinoembryonic antigen (CEA) abnormal proportion and cancer rate. In terms of the prevalence of pulmonary hypertension, the CPFE group (41.7%) > the COPD group (33.1%) > the ILD group (32.9%) was shown, but no statistical significance was found among the three groups.ConclusionsMale and smoking are not only risk factors for COPD but also for CPFE. At the same time, the suffering of CPFE may be affected by immune factors and hyperlipidemia. The proportion of CPFE patients complicated with cancer and CEA abnormalities is higher than COPD patients. The severity of pulmonary hypertension in CPFE patients is significantly higher than the other two diseases.
ObjectiveTo explore the relevance of the ratio of pulmonary arterial diameter to aortic diameter exceeding one (PA:A>1) with brain natriuretic peptide (BNP) and inflammatory factor levels in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). MethodsFrom August 2013 to December 2013,95 inpatients with AECOPD in West China Hospital were divided into two groups according to the ratio of pulmonary arterial diameter to aortic diameter. The clinical data of the patients were collected. Meanwhile,arterial blood gas,plasma levels of BNP,C-reactive protein (CRP),and interleukin-6 (IL-6) within 24 hours were measured. ResultsThe plasma BNP level was 2005(483-4582)ng/L in the group with PA:A>1,and 404(137-1224)ng/L in the group with PA:A<1. There was significant difference in plasma BNP level between two groups (P<0.01). There was no significant difference in CRP or IL-6 level between two groups (P>0.05). ConclusionThe ratio of pulmonary arterial diameter to aortic diameter is correlated with BNP level in patients with AECOPD,but is not correlated with CRP or IL-6.
Pulmonary hypertension is a kind of progressive pulmonary vascular diseases in which there is excessive vasoconstriction and abnormal pulmonary vascular remodeling, and then a gradual increase in pulmonary arterial pressure, and it eventually leads to right ventricular failure and even death. The pathogenesis of pulmonary hypertension is still uncertain, but some studies suggest that Hippo pathway or some components of the Hippo pathway may be involved in the progress of pulmonary hypertension. In this review, we describe the mechanism of the Hippo pathway or some components of the Hippo pathway in the progress of pulmonary hypertension.
ObjectiveTo observe the relationship of serum tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and C-reactive protein (CRP) with obstructive sleep apnea hypopnea syndrome (OSAHS) associated pulmonary hypertension (OSAHS-PH). MethodsFrom September 2013 to October 2014, 38 OSAHS patients, 32 OSAHS-PH patients and 35 healthy subjects were enrolled from the General Hospital of Ningxia Medical University. OSAHS was diagnosed by polysomnography. The pulmonary artery systolic pressure (PASP) was measured by echocardiograph, and the diagnose criteria for pulmonary hypertension was PASP≥40 mm Hg. Serum TNF-α, IL-6, CRP and endothelin 1 (ET-1) were detected by enzyme-linked immunosorbent assay. The correlation between TNF-α, IL-6, CRP, ET-1 and PASP was analyzed. ResultsThe serum levels of TNF-α, IL-6, CRP and ET-1 were remarkably different among three groups (F=55.34, 25.05, 23.85, 34.06 respectively; all P < 0.05). The levels of TNF-α, IL-6, CRP and ET-1 in the OSAHS group were higher than those in the healthy group, and lower than those in the OSAHS-PH group (all P < 0.05). The PASP was positively correlated with the levels of the four factors (r=0.755, 0.762, 0.747, 0.759 respectively; all P < 0.01). ConclusionThe levels of serum TNF-α, IL-6 and CRP are correlated with pulmonary hypertension and they may be involved in the process of OSAHS-PH.
Objective To investigate independent prognostic factors influencing the prognosis of connective tissue disease-associated interstitial lung disease with pulmonary hypertension (CTD-ILD-PH), and construct a nomogram model using machine learning to predict 1-, 3- and 5-year mortality risks, providing evidence for clinical diagnosis and treatment. Methods Patients diagnosed with CTD-ILD-PH and treated at the First Affiliated Hospital of Zhengzhou University from February 2011 to June 2021 were screened. The least absolute shrinkage and selection operator (Lasso), univariate Cox regression, and multivariate Cox regression analyses were combined to identify independent prognostic factors for CTD-ILD-PH patients. A novel nomogram prognostic model was constructed and internally validated using 1000 bootstrap resamples. The receiver operating characteristic (ROC) curve and Harrell's C-index assessed the predictive performance of the model. Calibration curves evaluated the model fit. Decision curve analysis (DCA) assessed the clinical utility of the model, and external validation was conducted using a separate test set. Results The study included 313 patients, with 108 deaths observed during the follow-up. Using the Lasso-Cox method, albumin, alanine aminotransferase (ALT), red cell volume distribution width (RDW), age, smoking history, rural residence, and pulmonary artery systolic pressure were identified as independent prognostic factors. The Harrell's C-index in the training set was 0.802, and the area under ROC curve was 0.880 (95%CI 0.833 - 0.928). Internal validation showed an average Harrell's C-index of 0.791. Calibration curves indicated high consistency between predicted and observed results. DCA confirmed the model's good clinical utility. External validation results demonstrated the model's favorable predictive performance and clinical utility. Conclusions Our research suggest that lower albumin, elevated ALT, elevated RDW, advanced age, smoking history, rural areas and higher pulmonary artery systolic blood pressure are independent prognostic risk factors for patients with CTD-ILD-PH. In this study, a prognostic model was developed for the first time to predict 1-, 3- and 5-year mortality in CTD-ILD-PH patients, which provides some reference value for future mortality risk assessment in CTD-ILD-PH.