Pulmonary Circulation最新文献

{"title":"The hepcidin-ferroportin axis influences mitochondrial function, proliferation, and migration in pulmonary artery endothelial and smooth muscle cells.","authors":"Theo Issitt, Quezia K Toe, Sofia L Pedersen, Thomas Shackshaft, Maziah Mohd Ghazaly, Laura West, Nadine D Arnold, Abdul Mahomed, George W Kagugube, Latha Ramakrishnan, Allan Lawrie, Gregory J Quinlan, S John Wort","doi":"10.1002/pul2.70006","DOIUrl":"10.1002/pul2.70006","url":null,"abstract":"<p><p>Elevated circulating hepcidin levels have been reported in patients with pulmonary artery hypertension (PAH). Hepcidin has been shown to promote proliferation of human pulmonary artery smooth muscle cells (PASMCs) in vitro, suggesting a potential role in PAH pathogenesis. However, the role of human pulmonary artery endothelial cells (PAECs) as either a source of hepcidin, or the effect of hepcidin on PAEC function is not as well described. The objective of this study was to define the role of the hepcidin-ferroportin axis on the phenotype of PAEC and to study potential PAEC-PASMC interactions relevant to the pathogenesis of pulmonary vascular remodeling and PAH. PAECs treated with hepcidin, or interleukin-6 were investigated for both ferroportin and hepcidin release and regulation using immunofluorescence, mRNA levels and cellular release assays. Effects of hepcidin on PASMC and PAEC mitochondrial function was investigated using immunofluorescence and seahorse assay. Migration and proliferation of PASMCs treated with conditioned media from hPAEC treated with hepcidin was investigated using the xCELLigence system and other tools. We demonstrate in this study that PAECs express ferroportin; hepcidin treatment of PAECs resulted in mitochondrial iron accumulation and intracellular hepcidin biosynthesis and release. Conditioned media from hepcidin treated PAECs caused PASMCs to down-regulate ferroportin expression whilst promoting migration and proliferation. Inhibition of hepcidin in PAEC conditioned media limited these responses. PASMC cellular and mitochondrial iron retention are associated with migratory and proliferative responses. This study confirms that the hepcidin ferroportin axis is present and operational in PAECs. Modulation of this axis shows distinct differences in responses seen between PAECS and PASMCs. Stimulation of this axis in PAECs with hepcidin may well institute proliferative and migratory responses in PASMCs of relevance to pathogenesis of PAH offering potential novel therapeutic targets.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70006"},"PeriodicalIF":2.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Sodium-Glucose Co-Transporter-2 Inhibitors on Exercise-Induced Pulmonary Hypertension.","authors":"Taijyu Satoh, Nobuhiro Yaoita, Satoshi Higuchi, Kotaro Nochioka, Saori Yamamoto, Haruka Sato, Shunsuke Tatebe, Kaito Yamada, Yusuke Yamada, Kohei Komaru, Naoki Chiba, Yuki Sarashina, Ryuichi Mori, Mitsuru Nakada, Hideka Hayashi, Hideaki Suzuki, Hiroyuki Takahama, Hideki Ota, Satoshi Yasuda","doi":"10.1002/pul2.70026","DOIUrl":"10.1002/pul2.70026","url":null,"abstract":"<p><p>Patients with borderline pulmonary hypertension (PH) often experience shortness of breath or exacerbation of PH during exercise, known as exercise-induced PH. However, the pathogenesis of exercise-induced post-capillary PH (post-EIPH) and its treatment strategies remain unclear. Recent guidelines and consensus documents have highlighted the benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors in heart failure and chronic kidney disease (CKD). This study aimed to investigate the effects of SGLT2 inhibitors in patients with post-EIPH and CKD. This single-center prospective cohort study enroled 10 patients with CKD (age, 68 years; female, 60%) who exhibited post-EIPH between 1 July 2022 and 31 December 2023. Post-EIPH was defined as a pulmonary capillary wedge pressure (PCWP)/cardiac output (CO) slope > 2 and peak PCWP during exercise ≥ 25 mmHg measured by catheterization. The patients received SGLT2 inhibitor treatment for 6 months. At rest, patients with post-EIPH had borderline-PH (21.5 ± 1.8 mmHg), with preserved left and right ventricular function. SGLT2 inhibitors treatment significantly reduced the PCWP/CO slope during exercise (3.9 ± 1.2 vs. 2.4 ± 1.2 mmHg/L/min, <i>p</i> = 0.013) and improved the 6-min walking distance (489.9 ± 80.2 vs. 568.3 ± 91.9 m, <i>p</i> = 0.014). Magnetic resonance imaging revealed a lower left ventricular global longitudinal strain in patients with post-EIPH, which was increased by SGLT2 inhibitor treatment (-13.8 ± 2.0 vs. -17.3 ± 2.0%, <i>p</i> = 0.003). SGLT2 treatment inhibitors mitigated post-EIPH hemodynamic abnormalities and exercise intolerance, suggesting their potential as its therapeutic option.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70026"},"PeriodicalIF":2.2,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Right ventricular stroke work index in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: A retrospective observational study.","authors":"Györgyi Csósza, Luca Valkó, Elek Dinya, György Losonczy, Veronika Müller, Zsófia Lázár, Kristóf Karlócai","doi":"10.1002/pul2.12433","DOIUrl":"10.1002/pul2.12433","url":null,"abstract":"<p><p>The right ventricular stroke work index (RVSWI) reflects the active work of the right ventricle (RV), but its clinical usefulness is not yet fully known in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to evaluate the correlation of RVSWI to clinical parameters, the presence of comorbidities and response to therapy. We performed a retrospective observational study of 54 patients (PAH: <i>N</i> = 30, CTEPH: <i>N</i> = 24) and control patients (<i>N</i> = 11), and collected clinical data including RVSWI and comorbidities at baseline. We also compared changes in the parameters of the four-strata mortality risk score at follow-up (median time of 12 months) after the initiation of therapy between patients with low- (<1450 mmHg*mL/m², <i>N</i> = 18) and high-RVSWI values (≥1450 mmHg*mL/m², <i>N</i> = 19). RVSWI at diagnosis was higher in PAH/CTEPH compared to control subjects (1408 ± 391 vs. 704 ± 140 mmHg*mL/m², <i>p</i> < 0.001, mean ± standard deviation, <i>t</i>-test), but did not differ between PAH and CTEPH patients (1406 ± 342 vs. 1409 ± 470 mmHg*mL/m², <i>p</i> = 0.98). Patients without comorbidities had higher RVSWI than those with comorbidities (<i>N</i> = 23: 1522 ± 400 vs. <i>N</i> = 31: 1323 ± 384 mmHg*mL/m², <i>p</i> = 0.04), which was also found in PAH (<i>p</i> < 0.001), but not in CTEPH (<i>p</i> = 0.37). A greater improvement in the four-strata mortality risk score (<i>p</i> < 0.05) and a trend for a larger reduction in N-terminal proB-type natriuretic peptide concentration (<i>p</i> = 0.06) were observed in the high-RVSWI subgroup than in the low-RVSWI patients at follow-up. In PAH and CTEPH, RVSWI provides additional information on RV function in comorbidities, and it may predict response to specific therapy. Regular monitoring of RVSWI may aid in optimizing therapy selection and timing.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e12433"},"PeriodicalIF":2.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synchrotron-Based Phase-Contrast Micro-CT Combined With Histology to Decipher Differences Between Hereditary and Sporadic Pediatric Pulmonary Veno-Occlusive Disease.","authors":"Ida Jeremiasen, Niccolò Peruzzi, Elna Lampei, Sofie Meyer, Levent M Akyürek, Erik Gebre-Medhin, Ceren Mutgan, Peter Dorfmüller, Lavinia Neubert, Danny Jonigk, Csaba Galambos, Karin Tran-Lundmark","doi":"10.1002/pul2.70024","DOIUrl":"10.1002/pul2.70024","url":null,"abstract":"<p><p>Pulmonary veno-occlusive disease (PVOD) is a lethal variant of pulmonary hypertension. The degree of pulmonary arterial involvement varies. Here, we compare two PVOD patients who were transplanted at 8 years of age, whereof one is a homozygous <i>EIF2AK4</i> mutation carrier. Tissue was imaged with synchrotron-based micro-CT and the results were compared with clinical data and sectioned tissue was analyzed with histology, immunohistochemistry, immunofluorescence, and in situ hybridization. Chest CT of the noncarrier exhibited scattered poorly defined ground-glass opacities and marked septal lines, whereas the mutation carrier showed numerous nodular centrilobular ground-glass opacities and sparse septal lines. The noncarrier developed pulmonary edema with vasodilators and 3D imaging combined with histology showed severe obstruction of interlobular septal veins and medial hypertrophy of pulmonary arteries, but no arterial or arteriolar intimal fibrosis. In contrast, the mutation carrier exhibited only mild intimal fibrosis in interlobular septal veins but severe arterial and arteriolar remodeling, including intimal fibrosis, tortuous course of arterioles, muscularization extending to the alveolar duct level and multiple vascular lumens within the same pulmonary arterial adventitia. Both patients had focally thickened alveolar septa with areas of pulmonary capillary hemangiomatosis (PCH) which colocalized with increased capillary muscularization, tenascin C expression, and deposition, as well as with matrix metalloproteinase-9 (MMP9)/CD45 positive cells. In conclusion, synchrotron-based phase-contrast micro-CT is valuable for understanding vascular remodeling. Significant differences were observed between heritable and sporadic PVOD, which may influence management strategies.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70024"},"PeriodicalIF":2.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening and diagnosis of pulmonary hypertension associated with chronic lung disease (PH-CLD): A consensus statement from the pulmonary vascular research institute's innovative drug development initiative-group 3 pulmonary hypertension.","authors":"P Vitulo, L Piccari, S J Wort, O A Shlobin, G Kovacs, C D Vizza, P M Hassoun, H Olschewski, R E Girgis, S M Nikkho, S D Nathan","doi":"10.1002/pul2.70005","DOIUrl":"10.1002/pul2.70005","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is a frequent complication of chronic lung disease (CLD). However, PH is difficult to diagnose early since accompanying symptoms overlap and are similar to those of the underlying CLD. In most cases the PH is mild to moderate and therefore physical signs may be absent or subtle. This consensus paper provides insight into the clues that might suggest the presence of occult PH in patients with CLD. An overview of current diagnostic tools and emerging diagnostic technologies is provided as well as guidance for the work-up and diagnosis of PH in patients with CLD.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70005"},"PeriodicalIF":2.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Same-Day Discharge Following Outpatient Balloon Pulmonary Angioplasty: A Single-Center Experience.","authors":"Amit Saha, Jeffrey P Chidester, Hurst M Hall, Trushil Shah, Kelly M Chin, Sonja D Bartolome, Thomas P Koshy","doi":"10.1002/pul2.70025","DOIUrl":"10.1002/pul2.70025","url":null,"abstract":"<p><p>Overnight inpatient monitoring is common following balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). We describe our institutional experience in same-day discharge (SDD) after BPA. Across 78 BPA sessions, there were only 2 (2.6%) admissions for hemoptysis with no reperfusion lung injury or deaths at 30 days.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70025"},"PeriodicalIF":2.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise pulmonary hypertension in chronic thromboembolic pulmonary disease: A right heart catheterization study.","authors":"Adam Dhayyat, Janne Mykland Hilde, Øyvind Jervan, Diyar Rashid, Jostein Gleditsch, Knut Stavem, Waleed Ghanima, Kjetil Steine","doi":"10.1002/pul2.70018","DOIUrl":"10.1002/pul2.70018","url":null,"abstract":"<p><p>Many patients with chronic thromboembolic pulmonary disease (CTEPD) suffer from exertional dyspnea. It is unclear if CTEPD is associated with exercise pulmonary hypertension (ePH). This cross-sectional study aimed to determine the occurrence of ePH in patients with CTEPD and to identify the haemodynamic changes during exercise. We recruited 36 patients with persistent dyspnoea and residual perfusion defects by ventilation/perfusion scintigraphy from a large cohort of patients with previous pulmonary embolism. All patients underwent exercise right heart catheterization before being classified into the following groups: (1) CTEPD without ePH; comprising patients with normal mean pulmonary artery pressure (mPAP) of ≤20 mmHg, but with mPAP/cardiac output (CO) slope of ≤3 mmHg/L/min, (2) CTEPD with ePH (CTEPD-ePH); those with CTEPD with an mPAP/CO slope of >3 mmHg/L/min, (3) chronic thromboembolic pulmonary hypertension (CTEPH); those with mPAP >20 mmHg, pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance >2 WU. The postcapillary contribution during exercise was considered present if the PAWP/CO slope of >2 mmHg/L/min. CTEPD without resting pulmonary hypertension (PH) was present in 29 (81%) of the 36 patients, of whom six (21%) had ePH, while five (14%) had CTEPH. Two patients had unclassified PH. Two (33%) of the six patients with CTEPD-ePH had a PAWP/CO slope of >2 mmHg/L/min, compared with two (40%) of the five of those with CTEPH. In conclusion, about 20% of patients with CTEPD and exertional dyspnoea had ePH. Exercise right heart catheterization revealed a notable proportion of patients with postcapillary contribution.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70018"},"PeriodicalIF":2.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THBS1 mediates hypoxia driven EndMT in pulmonary hypertension.","authors":"Bingming Peng, Yingzhen Zhou, Xingmeng Fu, Li Chen, Zhengxia Pan, Qijian Yi, Tengteng Zhao, Zhou Fu, Ting Wang","doi":"10.1002/pul2.70019","DOIUrl":"10.1002/pul2.70019","url":null,"abstract":"<p><p>Long-term hypoxia is one of the main causes of pulmonary vascular remodeling in pulmonary hypertension (PH) associated with congenital heart disease (CHD) children. Endothelial to mesenchymal transition (EndMT) is an important pathological basis of pulmonary vascular remodeling in PH. We observed that Fibronectin 1 (FN1) had strong protein-protein interactions with both Thrombospondin 1 (THBS1) and Transglutaminase 2 (TGM2) in PH with venous peripheral bloods samples from pediatric patients and healthy children. LungMAP CellCards and heatmaps of human PAEC in PH patients and lung tissues in hypoxia induced PH mice model were used to show that THBS1 and FN1 were significantly elevated. We studied the relationship between THBS1 and FN1 in vivo, by using SUHX-induced PH mice model, and in vitro, by using hypoxia-induced human PAEC. The results showed that hypoxia could result in EndMT and inhibiting THBS1 could reverse EndMT in vivo and in vitro, verifying our transcriptome results. Taken together, our research demonstrated that THBS1 could mediate hypoxia driven EndMT of PH, providing a new insight of research in the pathophysiology of PH.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70019"},"PeriodicalIF":2.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOPRANO: Macitentan in patients with pulmonary hypertension following left ventricular assist device implantation.","authors":"Robert P Frantz, Shashank S Desai, Gregory Ewald, Veronica Franco, Antoine Hage, Evelyn M Horn, Shane J LaRue, Michael A Mathier, Stacy Mandras, Myung H Park, Ashwin K Ravichandran, Joel D Schilling, I-Wen Wang, Ronald Zolty, Gabriela Gomez Rendon, Mark A Rocco, Mona Selej, Carol Zhao, J Eduardo Rame","doi":"10.1002/pul2.12446","DOIUrl":"10.1002/pul2.12446","url":null,"abstract":"<p><p>Macitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group study. Patients with an LVAD implanted within the prior 90 days who had persistent PH (i.e., mean pulmonary arterial pressure ≥25 mmHg, pulmonary artery wedge pressure [PAWP] ≤18 mmHg, and pulmonary vascular resistance [PVR] >3 Wood units [WU]) were randomized (1:1) to macitentan 10 mg or placebo once daily for 12 weeks. The primary endpoint was change in PVR. Secondary endpoints included change in right-heart catheterization hemodynamic variables, N-terminal prohormone of brain natriuretic peptide levels, World Health Organization functional class, and safety/tolerability. Fifty-seven patients were randomized to macitentan (<i>n</i> = 28) or placebo (<i>n</i> = 29). A statistically significant reduction in PVR from baseline to Week 12 was observed with macitentan versus placebo (placebo-corrected geometric mean ratio, 0.74; 95% confidence interval, 0.58-0.94; <i>p</i> = .0158). No statistically significant differences were observed in secondary endpoints. In a post-hoc analysis, 66.7% of patients receiving macitentan achieved PVR <3 WU versus 40.0% receiving placebo (<i>p</i> = .0383). Macitentan was generally well tolerated; adverse events were consistent with those in previous PAH studies with macitentan. In conclusion, macitentan showed promising tolerability and significantly reduced PVR in PH patients with persistently elevated PVR after LVAD implantation. ClinicalTrials. gov identifier: NCT02554903.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e12446"},"PeriodicalIF":2.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary vascular manifestations of hereditary haemorrhagic telangiectasia.","authors":"Sarah Cullivan, Barry Kevane, Brian McCullagh, Terry M O'Connor, Robin Condliffe, Sean Gaine","doi":"10.1002/pul2.70007","DOIUrl":"10.1002/pul2.70007","url":null,"abstract":"<p><p>Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant, multisystem disorder that manifests with a spectrum of disease including cardiopulmonary complications. HHT is characterised by aberrant signalling via the transforming growth factor β (TGFβ) pathway, with loss of vascular integrity, angiogenesis and vascular dysplasia. The disease has an estimated prevalence of 1 in 5000 persons and the penetrance increases with increasing age. HHT commonly presents with epistaxis and telangiectasia, while visceral arteriovenous malformations are not uncommon. Mutations in the ENG, ACVRL1 and MADH4 genes account for 97% of all HHT cases, and it is recommended that genetic tests are used in combination with the clinical Curaçao criteria to confirm the diagnosis. HHT can be complicated by significant pulmonary vascular disease including pulmonary arteriovenous malformations, pulmonary arterial hypertension and high output cardiac failure. These are associated with substantial morbidity and mortality and therefore timely diagnosis is important to mitigate complications and optimise preventative strategies. This article outlines important advances in our understanding of the pathobiology of HHT and current recommendations regarding the diagnosis and screening of HHT with a specific focus on adult patients with pulmonary vascular disease. Important therapeutic advances, novel therapies on the horizon and unmet needs are also explored.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70007"},"PeriodicalIF":2.2,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11586239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}