Pulmonary hypertension is a disease characterized by pulmonary artery pressure increased, with or without small artery pathological change, which ultimately leads to right heart failure or even death. Pulmonary hypertension seriously threatens to human health, however, the pathogenesis of pulmonary hypertension is unclear. Previous studies have found that bone morphogenetic protein (BMP) signaling system played an important role in the progress of pulmonary hypertension. In the current review, we describe the mechanism of BMP4 in the development of pulmonary hypertension.
Pulmonary hypertension (PH), characterized by diverse etiologies and intricate pathological mechanisms, is a complex cardiopulmonary vascular disorder featuring high morbidity and mortality. Percutaneous pulmonary artery denervation (PADN) represents an emerging interventional treatment method, which shows good prospects in the clinical practice of PH. The PADN has attained preliminary achievements in terms of safety and efficacy. Nevertheless, its long-term prognosis, the characteristics of the appropriate patient populations, and the optimization strategies combined with targeted pharmacotherapy remain to be further explored. This article reviews the current clinical applications of PADN as well as the challenges it confronts.
In left heart disease, pulmonary artery pressure would increase due to the elevated left atrial pressure. This type of pulmonary hypertension (PH) is belonged to type Ⅱ as a passive PH (pPH) in its classification. The essential cause of pPH is excessive blood volume. Recently, we have identified another type of pPH, which is induced by vasopressors. Vasopressor-induced pPH shares similar pathophysiological manifestations with left heart disease-induced pPH. pPH would, therefore, be aggressive if vasopressors were applied in patients with left heart disease, which may be common after cardiac surgery, because heart undergoing surgical trauma may require support of vasopressors. Unfortunately, pPH after cardiac surgery is often ignored because of the difficulty in diagnosis. To improve the understanding of pPH and its effect on outcomes, here we highlight the mechanisms of interaction between vasopressor-induced and left heart failure-induced pPH, and provide insights into its therapeutic options.
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.
Pulmonary hypertension due to left heart disease (PH-LHD) is the most common in various types of pulmonary hypertension. Although there are many treatments for pulmonary hypertension, it may be harmful when we adopt treatment without detrimental diagnosis and classification of pulmonary hypertension. Therefore, it is very crucial to have accurate diagnosis and classification of pulmonary hypertension before making treatment decisions. However, there are still some difficulties in the classification of pulmonary hypertension in clinical work. It is a great challenge with limited treatment to solve the PH-LHD which often has complicated pathophysiological mechanisms of precapillary and postcapillary pulmonary hypertension. Here, we review the research status of PH-LHD.
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.
Abstract： Right ventricular dysfunction or right heart failure is a complex clinical syndrome and often leads to a poor prognosis and high mortality. In order to detect right ventricular dysfunction at an early stage, provide a therapy guidance and evaluate treatment outcomes， right ventricular function evaluation has aroused more and more concern in clinical physicians. With the advantages of being non-invasive， accuracy and repetitiveness， echocardiography is used extensively in the assessment of heart function. In this review， we focus on how to use echocardiography to evaluate right ventricular function easily, efficiently， accurately and sensitively， and provide a good foundation for its further clinical application.
ObjectiveTo summarize the clinical characteristics and the long-term results of pulmonary thromboendarterectomy (PTE) in the chronic thromboembolic pulmonary hypertension (CTEPH) patients with unilateral main pulmonary artery occlusion.MethodsWe retrospectively analyzed the clinical data of 15 CTEPH patients with unilateral main pulmonary artery occlusion in Fuwai Hospital between 2004 and 2018. There were 11 males and 4 females aged 34.1±12.0 years at operation.ResultsThe mean circulatory arrest was 31.1±12.1 minutes. The ICU stay was 5 (2-29) d. The hospital stay was 15 (8-29) d. There was no hospital death. There was a decline in systolic pulmonary artery pressures (sPAP, 69.9±27.9 mm Hg to 35.1±9.7 mm Hg, P=0.020) after surgery. On postoperative V/Q scan, only 6 patients (40.0%) had significant improvement in reperfusion (≥75% estimated) of the occluded lung. There was no death during the median observation period of 49 months follow-up, while 2 patients had recurrence of pulmonary embolism.ConclusionCTEPH patients with unilateral main pulmonary artery occlusion represent a challenging cohort. PTE is a curative resolution in both early- and long- term results, although there is a high requirement of perioperative management and a high risk of postoperative complications and rethrombosis.
Objective To detecting the genetic etiology of a family with idiopathic pulmonary arterial hypertension and make gene diagnosis for the patient, so as to guide the targeted treatment and early intervention for the patient and her families. Methods The phenotype information of the family members was reviewed and their peripheral blood was collected for genomic DNA extraction. Exome sequencing was used to screen the mutations and proving the selected mutations by PCR-Sanger sequencing method. The pathogenicity of candidate mutation sites were searched through PubMed and related databases, and analyzed by protein function software. The judgement of pathogenicity was considered by clinical presentations and sequencing results of the patients based on Standards and guidelines for the interpretation of sequence variants revised by ACMG. Results At present, there was only one patient with pulmonary hypertension in this family, and other family members had no clinical manifestations of pulmonary hypertension. The female patient had BMPR2 gene c.1748dupA(p.Asn583Lysfs*6) heterozygous mutant. Her father and second son had BMPR2 gene c.1748dupA(p.Asn583Lysfs*6) heterozygous mutant, but none of the other members of the family had the mutation. Conclusions The heterozygous mutation of c.1748dupA (p.Asn583Lysfs*6) of BMPR2 gene is the genetic cause of the idiopathic pulmonary arterial hypertension patient, and the clinical significance of c.1748dupA(p.Asn583Lysfs*6) is pathogenic. The patient can be further diagnosed as pulmonary hypertension, primary 1 (PPH1) by gene diagnosis, and the mutant is novel and pathogenic for PPH1.
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.
