Pulmonary Circulation最新文献

Recent reports have revealed a substantial morbidity burden associated with "post-PE syndrome" (PPES). Cardiopulmonary exercise testing (CPET) has shown promise in better characterizing these patients. In this systematic review and pooled analysis, we aim to use CPET data from PE survivors to understand PPES better. A literature search was conducted in PubMed, EMBASE, and Cochrane for studies reporting CPET results in post-PE patients without known pulmonary hypertension published before August 1, 2023. Studies were independently reviewed by two authors. CPET findings were subcategorized into (1) exercise capacity (percent predicted pVO₂ and pVO₂) and (2) ventilatory efficiency (VE/VCO₂ slope and V_D/V_T). We identified 14 studies (n = 804), 9 prospective observational studies, 4 prospective case-control studies, and 1 randomized trial. Pooled analysis demonstrated a weighted mean percent predicted pVO₂ of 76.09 ± 20.21% (n = 184), with no difference between patients tested <6 months (n = 76, 81.69±26.06%) compared to ≥6 months post-acute PE (n = 88, 82.55 ± 21.47%; p = 0.817). No difference was seen in pVO₂ in those tested <6 months (n = 76, 1.67 ± 0.51 L/min) compared to ≥6 months post-acute PE occurrence (n = 144, 1.75 ± 0.57 L/min; p = 0.306). The weighted mean VE/VCO₂ slope was 32.72 ± 6.02 (n = 244), with a significant difference noted between those tested <6 months (n = 91, 36.52 ± 6.64) compared to ≥6 months post-acute PE (n = 191, 31.99 ± 5.7; p < 0.001). In conclusion, this study, which was limited by small sample sizes and few multicenter studies, found no significant difference in exercise capacity between individuals tested <6 months versus ≥6 months after acute PE. However, ventilatory efficiency was significantly improved in patients undergoing CPET ≥ 6 months compared to those <6 months from the index PE.

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 ^+/- mice spontaneously developed PH and right ventricular hypertrophy (RVH), associated with increased EndoMT markers and decreased EC markers. Interestingly, chronic hypoxia exacerbated right ventricular systolic pressure and RVH in Etv2 ^+/- mice. PPARγ transcriptionally activates the ETV2 promoter. Consistently, while mice overexpressing endothelial PPARγ increases the expression of ETV2 and endothelial markers with reduced EndoMT markers, endothelial PPARγ KO mice show decreased ETV2 expression and enhanced EndoMT markers. Inducible overexpression of ETV2 under induced-EndoMT cell model reduces number of cells with mesenchymal morphology and decreases expression of mesenchymal markers with increased EC makers, compared to control. Therefore, our study suggests that PPARγ-ETV2 signaling regulates PH pathogenesis through EndoMT.

This research aims to investigate the impact of Didang decoction (DD) on the formation of neutrophil extracellular traps (NETs) and cancer-associated thrombosis in lung cancer. BALB/c nude mice were used to establish xenograft models for inducing deep vein thrombosis. Tumor growth and thrombus length were assessed. The impact of DD on NET generation was analyzed using enzyme-linked immunosorbent assay, immunofluorescence staining, quantitative real-time PCR, and western blot analysis, both in vivo and in vitro. CI-amidine, a PAD4 inhibitor, was employed to evaluate the role of PAD4 in the generation of NETs. In vivo studies demonstrated that treatment with DD reduced tumor growth, inhibited thrombus formation, and decreased the levels of NET markers in the serum, tumor tissues, neutrophils, and thrombus tissues of mice. Additional data indicated that DD could suppress neutrophil counts, the release of tissue factor (TF), and the activation of thrombin-activated platelets, all of which contributed to increased formation of NETs in mouse models. In vitro, following incubation with conditioned medium (CM) derived from Lewis lung carcinoma cells, the expression of NET markers in neutrophils was significantly elevated, and an extracellular fibrous network structure was observed. Nevertheless, these NET-associated changes were partially counteracted by DD. Additionally, CI-amidine reduced the expression of NET markers in CM-treated neutrophils, consistent with the effects of DD. Collectively, DD inhibits cancer-associated thrombosis in lung cancer by decreasing PAD4-dependent NET formation through the regulation of TF-mediated thrombin-platelet activation. This presents a promising therapeutic strategy for preventing and treating venous thromboembolism in lung cancer.

Endothelial dysfunction is an underlying mechanism for the development of pulmonary arterial hypertension (PAH). Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF) may help repair the dysfunctional endothelium and provide treatment for PAH. To examine this possibility, nanoparticles carrying human recombinant VEGF and SDF (VEGFNP and SDFNP) were aerosolized into the lungs of nude rats at Day 14 after monocrotaline (MCT) injection and analyses were performed at Day 28. The data show that the VEGFNP/SDFNP delivery led to a lower pulmonary arterial pressure and prevented right ventricular hypertrophy in the MCT rats: the right ventricular systolic pressure of the control, MCT, and MCT + VEGFNP/SDFNP treatment groups were 29±2, 70±9, and 44±5 (mean±SD) mmHg, respectively; the pulmonary vascular resistance indices of the groups were 0.6±0.3, 3.2±0.7, and 1.7±0.5, respectively; and the Fulton indices [-RV/(LV + Septum)] were 0.22±0.01, 0.44±0.07, and 0.23±0.02, respectively. The VEGFNP/SDFNP delivery delayed the thickening of distal pulmonary vessels: the number of nearly occluded vessels in a whole lung section from the MCT and MCT + VEGFNP/SDFNP groups were 46±12 and 2±3, respectively. Gene expression analysis of the endothelial cell markers, VE-cadherin, KDR, BMPR2, and eNOS, and smooth cell markers, SM-MHC and α-SMA, indicated significant loss of distal pulmonary vessels in the MCT- treated rats. VEGFNP/SDFNP delivery did not recover the loss, but significantly increased eNOS and decreased α-SMA expression in the MCT-treated lungs. Thus, the therapeutic effect of VEGFNP/SDFNP may be mediated by improving/repairing endothelial function in the PAH lungs.

Right ventricle (RV)-to-pulmonary artery (PA) coupling measured by the ratio of echocardiography-derived tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) is a meaningful prognostic marker in pulmonary hypertension (PH). It's unclear if balloon pulmonary angioplasty (BPA) treatment of chronic thromboembolic pulmonary hypertension (CTEPH) alters RV-PA coupling measured by TAPSE/PASP. We reviewed CTEPH patients treated with BPA at our institution who had a transthoracic echocardiogram (TTE) before BPA and a follow-up TTE at any point during BPA. TAPSE was obtained from the initial and lattermost TTE; hemodynamics were obtained before each BPA session. Between March 2015 to October 2023, there were 228 patients treated with BPA. After excluding post-PTE patients and those without PH, 67 were included. Initial TAPSE/PASP was 0.39 ± 0.21 mm/mmHg. Using previously defined TAPSE/PASP tertiles in PH (<0.19, 0.19-0.32, >0.32 mm/mmHg), there were 6 patients (9%) in low, 30 (45%) in middle, and 31 (46%) in the high tertiles at baseline. The lower TAPSE/PASP tertiles had more severe baseline hemodynamics (p < 0.001) compared to the high TAPSE/PASP cohort. At follow-up, TAPSE/PASP improved to 0.47 ± 0.20 mm/mmHg (p = 0.023), with 2 (3%), 13 (19%), and 52 (78%) patients in the low, middle, high TAPSE/PASP tertiles, respectively. As patients progress through BPA sessions, the TAPSE/PASP ratio increases, possibly reflecting improved RV mechanics and RV-PA coupling. TAPSE/PASP ratio as a marker of RV-PA coupling can improve with BPA treatment and may be an important measure to follow during treatment of CTEPH.

The PERFECT study, a randomized, controlled, double-blind study of inhaled treprostinil in patients with COPD and associated pulmonary hypertension (PH-COPD) was a negative trial that was terminated early. The reason(s) for the negative outcome remains uncertain. A post hoc analysis of data from the PERFECT study was undertaken to identify adverse responders and possibly potential responders. The goal was also to provide insight into phenotypes for possible inclusion and exclusion in future PH-COPD clinical trials. An adverse response on active treatment was seen in 36.4% (24/66) of the subjects compared to 27.6% (16/58) on placebo. There was no evidence to suggest that hyperinflation, bronchospasm, or occult heart failure played any role in the untoward outcomes of the study. The patients who died during the study all had baseline diffusing capacity for carbon monoxide ≤25% of predicted. Evidence of a potential response was seen in 10.6% (7/66) of the patients who received inhaled treprostinil. Patients who had evidence of a treatment response had a baseline mean pulmonary artery pressure of ≥40 mmHg and a forced expiratory volume in the first second of ≥40%. Change in N-terminal prohormone of brain natriuretic peptide did not predict clinical response. This post hoc analysis provides information that may potentially enable improved selection of patients for future therapeutic trials in PH-COPD. These analyses are post hoc, observational, and exploratory. The thresholds defining the spectrum of responders are preliminary and may require further refinement and validation in future studies.

Exercise training is recommended for pulmonary hypertension (PH). Post hoc analysis of the PH and Home-Based (PHAHB) trial stratified patients into two groups based on median diffusing capacity of the lungs for carbon monoxide (DLCO). Patients with higher DLCO had a greater improvement in physical activity performance in response to exercise training, compared to those with lower DLCO. DLCO may be an important consideration in prescribing exercise in PH.

We present the case of an 18-year-old woman with a 5-day history of thoracic pain and dyspnea following physical exertion, along with swelling of her right calf. Computertomography (CT) angiography confirmed a massive central pulmonary artery embolism (PE) of the left main branch. The patient underwent catheter-directed thrombolysis. Six months later, CT angiography revealed a postthrombotic subtotal blockage of the left pulmonary artery, resulting in hyperinflation of the right lung and right heart hypertrophy. Right heart catheterization identified a pulmonary artery mean pressure of 9 mmHg, which led to the diagnosis of chronic thromboembolic pulmonary disease (CTED). Pulmonary angiography confirmed the complete occlusion of the left pulmonary artery. The patient was referred to an International Reference Center for chronic thromboembolic pulmonary hypertension (CTEPH). There, she underwent pulmonary thrombendarterectomy of the affected pulmonary artery without complications. One-year follow-up has been postponed due to the recent surgery. The prevalence of CTEPH is reported at 8.4%, while CTED is observed in only 4% of survivors of PE cases. Patients experiencing unexplained dyspnea should be evaluated promptly for these conditions, warranting early diagnostic intervention.

Chronic thromboembolic pulmonary hypertension (CTEPH) is marked by persistent blood clots in pulmonary arteries, leading to significant morbidity and mortality. Emerging evidence highlights the role of microRNAs (miRNAs) in pulmonary hypertension, though findings on miRNA expression in CTEPH remain limited and inconsistent. This systematic review evaluates miRNA expression changes in CTEPH and their direction. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we registered our protocol in International Prospective Register of Systematic Reviews (CRD42024524469). We included studies on miRNA expression in CTEPH with comparative or analytical designs, excluding nonhuman studies, interventions, non-English texts, conference abstracts, and editorials. Databases searched included PubMed, EMBASE, Scopus, CENTRAL, and ProQuest. The Quality Assessment of Diagnostic Accuracy Studies-2 tool assessed bias risk, and results were synthesized narratively. Of 313 unique studies, 39 full texts were reviewed, and 9 met inclusion criteria, totaling 235 participants. Blood samples were analysed using quantitative real time polymerase chain reaction. Seven miRNAs (miR-665, miR-3202, miR-382, miR-127, miR-664, miR-376c, miR-30) were uniformly upregulated, while nine (miR-20a-5p13, miR-17-5p, miR-93-5p, miR-22, let-7b, miR-106b-5p, miR-3148, miR-320-a, miR-320b) were downregulated in CTEPH patients. Two upregulated miRNAs (miR-127 and miR-30a) were consistently associated with previous evidence in the mechanism inducing the development of CTEPH, and five downregulated miRNAs (miR-20-a, miR-17-5p, miR-93-5p, let-7b, miR-106b-5p) were associated with a protective effect against CTEPH. We also identified gaps in the literature where the evidence for five upregulated miRNAs (miR-665, miR-3202, miR-382, miR-664 and miR-376c) and four downregulated miRNAs (miR-22, miR-3148, miR-320-a, and miR-320b) in CTEPH is conflicting. Our findings offer insights into the role of miRNAs in CTEPH and underscore the need for further research to validate these miRNAs as biomarkers or therapeutic targets.