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Respiratory Research Nov 2023Pulmonary arterial hypertension (PAH), Group 1 pulmonary hypertension (PH), is a type of pulmonary vascular disease characterized by abnormal contraction and remodeling... (Review)
Review
BACKGROUND
Pulmonary arterial hypertension (PAH), Group 1 pulmonary hypertension (PH), is a type of pulmonary vascular disease characterized by abnormal contraction and remodeling of the pulmonary arterioles, manifested by pulmonary vascular resistance (PVR) and increased pulmonary arterial pressure, eventually leading to right heart failure or even death. The mechanisms involved in this process include inflammation, vascular matrix remodeling, endothelial cell apoptosis and proliferation, vasoconstriction, vascular smooth muscle cell proliferation and hypertrophy. In this study, we review the mechanisms of action of prostaglandins and their receptors in PAH.
MAIN BODY
PAH-targeted therapies, such as endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, activators of soluble guanylate cyclase, prostacyclin, and prostacyclin analogs, improve PVR, mean pulmonary arterial pressure, and the six-minute walk distance, cardiac output and exercise capacity and are licensed for patients with PAH; however, they have not been shown to reduce mortality. Current treatments for PAH primarily focus on inhibiting excessive pulmonary vasoconstriction, however, vascular remodeling is recalcitrant to currently available therapies. Lung transplantation remains the definitive treatment for patients with PAH. Therefore, it is imperative to identify novel targets for improving pulmonary vascular remodeling in PAH. Studies have confirmed that prostaglandins and their receptors play important roles in the occurrence and development of PAH through vasoconstriction, vascular smooth muscle cell proliferation and migration, inflammation, and extracellular matrix remodeling.
CONCLUSION
Prostacyclin and related drugs have been used in the clinical treatment of PAH. Other prostaglandins also have the potential to treat PAH. This review provides ideas for the treatment of PAH and the discovery of new drug targets.
Topics: Humans; Prostaglandins; Pulmonary Arterial Hypertension; Receptors, Prostaglandin; Vascular Remodeling; Familial Primary Pulmonary Hypertension; Epoprostenol; Prostaglandins I; Inflammation; Pulmonary Artery
PubMed: 37915044
DOI: 10.1186/s12931-023-02559-3 -
European Respiratory Review : An... Sep 2023Pulmonary hypertension (PH) is a progressive disease characterised by elevated pulmonary arterial pressure and right-sided heart failure. While conventional drug... (Review)
Review
Pulmonary hypertension (PH) is a progressive disease characterised by elevated pulmonary arterial pressure and right-sided heart failure. While conventional drug therapies, including prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors, have been shown to improve the haemodynamic abnormalities of patients with PH, the 5-year mortality rate remains high. Thus, novel therapies are urgently required to prolong the survival of patients with PH. Stem cell therapies, including mesenchymal stem cells, endothelial progenitor cells and induced pluripotent stem cells, have shown therapeutic potential for the treatment of PH and clinical trials on stem cell therapies for PH are ongoing. This review aims to present the latest preclinical achievements of stem cell therapies, focusing on the therapeutic effects of clinical trials and discussing the challenges and future perspectives of large-scale applications.
Topics: Humans; Hypertension, Pulmonary; Endothelin Receptor Antagonists; Cell- and Tissue-Based Therapy
PubMed: 37758272
DOI: 10.1183/16000617.0112-2023 -
Seminars in Thrombosis and Hemostasis Nov 2023Survivors of acute pulmonary embolism (PE) are at risk of developing persistent, sometimes disabling symptoms of dyspnea and/or functional limitations despite adequate... (Review)
Review
Survivors of acute pulmonary embolism (PE) are at risk of developing persistent, sometimes disabling symptoms of dyspnea and/or functional limitations despite adequate anticoagulant treatment, fulfilling the criteria of the post-PE syndrome (PPES). PPES includes chronic thromboembolic pulmonary hypertension (CTEPH), chronic thromboembolic pulmonary disease, post-PE cardiac impairment (characterized as persistent right ventricle impairment after PE), and post-PE functional impairment. To improve the overall health outcomes of patients with acute PE, adequate measures to diagnose PPES and strategies to prevent and treat PPES are essential. Patient-reported outcome measures are very helpful to identify patients with persistent symptoms and functional impairment. The primary concern is to identify and adequately treat patients with CTEPH as early as possible. After CTEPH is ruled out, additional diagnostic tests including cardiopulmonary exercise tests, echocardiography, and imaging of the pulmonary vasculature may be helpful to rule out non-PE-related comorbidities and confirm the ultimate diagnosis. Most PPES patients will show signs of physical deconditioning as main explanation for their clinical presentation. Therefore, cardiopulmonary rehabilitation provides a good potential treatment option for this patient category, which warrants testing in adequately designed and executed randomized trials. In this review, we describe the definition and characteristics of PPES and its diagnosis and management.
Topics: Humans; Chronic Disease; Risk Factors; Pulmonary Embolism; Acute Disease; Comorbidity; Hypertension, Pulmonary
PubMed: 35820428
DOI: 10.1055/s-0042-1749659 -
Seminars in Respiratory and Critical... Dec 2023Pulmonary hypertension (PH) is a pathophysiological manifestation of a heterogeneous group of diseases characterized by abnormally elevated pulmonary arterial pressures...
Pulmonary hypertension (PH) is a pathophysiological manifestation of a heterogeneous group of diseases characterized by abnormally elevated pulmonary arterial pressures diagnosed on right heart catheterization. The 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) Guidelines for the diagnosis and treatment of PH provides a new hemodynamic definition to define PH by lowering the threshold of the mean pulmonary artery pressure (mPAP) to 20 mm Hg. Precapillary PH is thus now defined as a mPAP >20 mm Hg together with a normal pulmonary artery wedge pressure (<15 mm Hg) and an increased pulmonary vascular resistance (>2 Wood Units). The ESC/ERS 2022 Guidelines also introduce a revised clinical classification of PH while retaining its previous distinction between the five groups according to the underlying pathophysiology.
Topics: Humans; Hypertension, Pulmonary; Hemodynamics; Cardiac Catheterization
PubMed: 37595614
DOI: 10.1055/s-0043-1770115 -
Cleveland Clinic Journal of Medicine Oct 2023Portopulmonary hypertension, ie, pulmonary arterial hypertension in a patient with portal hypertension, affects transplant eligibility and has a poor prognosis. The... (Review)
Review
Portopulmonary hypertension, ie, pulmonary arterial hypertension in a patient with portal hypertension, affects transplant eligibility and has a poor prognosis. The pathogenesis remains an area of active research, with various mechanisms proposed. Diagnosing it requires a detailed history, physical examination, laboratory tests, and echocardiographic evaluation, followed by a careful hemodynamic assessment.
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hypertension, Portal; Hemodynamics; Echocardiography
PubMed: 37783493
DOI: 10.3949/ccjm.90a.23023 -
Clinics in Chest Medicine Sep 2023The current approach for the management of pulmonary arterial hypertension (PAH) relies on data gathered from clinical trials and large registries. However, there is... (Review)
Review
The current approach for the management of pulmonary arterial hypertension (PAH) relies on data gathered from clinical trials and large registries. However, there is concern that minorities including Black, Indigenous, and People of Color are underrepresented in these trials and registries, making current data not generalizable to these groups of patients. Hence, it is important to discuss the significance of race/ethnicity and socioeconomic factors in patients with PAH. Here, we review the current knowledge on health care disparities in PAH. We also propose future steps in the global task of assuring justice and equality in access to pulmonary hypertension health care.
Topics: Humans; Pulmonary Arterial Hypertension; Healthcare Disparities; Hypertension, Pulmonary
PubMed: 37517834
DOI: 10.1016/j.ccm.2023.03.010 -
Pneumologie (Stuttgart, Germany) Nov 2023Chronic thromboembolic pulmonary disease (CTEPD) is an important late complication of acute pulmonary embolism, in which the thrombi transform into fibrous tissue,...
Chronic thromboembolic pulmonary disease (CTEPD) is an important late complication of acute pulmonary embolism, in which the thrombi transform into fibrous tissue, become integrated into the vessel wall, and lead to chronic obstructions. CTEPD is differentiated into cases without pulmonary hypertension (PH), characterized by a mean pulmonary arterial pressure up to 20 mmHg and a form with PH. Then, it is still referred to as chronic thromboembolic pulmonary hypertension (CTEPH).When there is suspicion of CTEPH, initial diagnostic tests should include echocardiography and ventilation/perfusion scan to detect perfusion defects. Subsequently, referral to a CTEPH center is recommended, where further imaging diagnostics and right heart catheterization are performed to determine the appropriate treatment.Currently, three treatment modalities are available. The treatment of choice is pulmonary endarterectomy (PEA). For non-operable patients or patients with residual PH after PEA, PH-targeted medical therapy, and the interventional procedure of balloon pulmonary angioplasty (BPA) are available. Increasingly, PEA, BPA, and pharmacological therapy are combined in multimodal concepts.Patients require post-treatment follow-up, preferably at (CTE)PH centers. These centers are required to perform a minimum number of PEA surgeries (50/year) and BPA interventions (100/year).
Topics: Humans; Hypertension, Pulmonary; Chronic Disease; Pulmonary Embolism; Lung; Pulmonary Artery
PubMed: 37963483
DOI: 10.1055/a-2145-4807 -
British Journal of Hospital Medicine... Aug 2023Post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension are two distinct clinical syndromes associated with adverse patient outcomes following a... (Review)
Review
Post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension are two distinct clinical syndromes associated with adverse patient outcomes following a venous thromboembolism. Clinical manifestations of post-thrombotic syndrome include persistent pain, swelling and ultimately venous ulceration following a deep venous thrombosis. Patients experiencing chronic thromboembolic pulmonary hypertension may have symptoms ranging from exertional dyspnoea to overt right heart failure. From a physician's perspective, the most effective preventative strategy is good quality anticoagulation for prophylaxis of primary and secondary venous thromboembolism. The treatment of post-thrombotic syndrome mainly involves lifestyle modifications alongside the use of elastic compression stockings while patients with chronic thromboembolic pulmonary hypertension should be offered targeted surgical and medical treatment options available at expert centres. Further research is warranted for both conditions to determine the role of direct oral anticoagulants when used with a preventive or therapeutic intent.
Topics: Humans; Hypertension, Pulmonary; Venous Thromboembolism; Dyspnea; Heart Failure; Life Style
PubMed: 37646549
DOI: 10.12968/hmed.2023.0114 -
International Journal of Biological... 2023Pulmonary and systemic hypertension (PH, SH) are characterized by vasoconstriction and vascular remodeling resulting in increased vascular resistance and... (Review)
Review
Pulmonary and systemic hypertension (PH, SH) are characterized by vasoconstriction and vascular remodeling resulting in increased vascular resistance and pulmonary/aortic artery pressures. The chronic stress leads to inflammation, oxidative stress, and infiltration by immune cells. Roles of metals in these diseases, particularly PH are largely unknown. This review first discusses the pathophysiology of PH including vascular oxidative stress, inflammation, and remodeling in PH; mitochondrial dysfunction and metabolic changes in PH; ion channel and its alterations in the pathogenesis of PH as well as PH-associated right ventricular (RV) remodeling and dysfunctions. This review then summarizes metal general features and essentiality for the cardiovascular system and effects of metals on systemic blood pressure. Lastly, this review explores non-essential and essential metals and potential roles of their dyshomeostasis in PH and RV dysfunction. Although it remains early to conclude the role of metals in the pathogenesis of PH, emerging direct and indirect evidence implicates the possible contributions of metal-mediated toxicities in the development of PH. Future research should focus on comprehensive clinical metallomics study in PH patients; mechanistic evaluations to elucidate roles of various metals in PH animal models; and novel therapy clinical trials targeting metals. These important discoveries will significantly advance our understandings of this rare yet fatal disease, PH.
Topics: Animals; Humans; Hypertension, Pulmonary; Pulmonary Artery; Lung; Hypertension; Inflammation; Ventricular Remodeling
PubMed: 37928257
DOI: 10.7150/ijbs.85590 -
Genetics of Pulmonary Pressure and Right Ventricle Stress Identify Diabetes as a Causal Risk Factor.Journal of the American Heart... Aug 2023Background Epidemiologic studies have identified risk factors associated with pulmonary hypertension and right heart failure, but causative drivers of pulmonary...
Background Epidemiologic studies have identified risk factors associated with pulmonary hypertension and right heart failure, but causative drivers of pulmonary hypertension and right heart adaptation are not well known. We sought to leverage unbiased genetic approaches to determine clinical conditions that share genetic architecture with pulmonary pressure and right ventricular dysfunction. Methods and Results We leveraged Vanderbilt University's deidentified electronic health records and DNA biobank to identify 14 861 subjects of European ancestry who underwent at least 1 echocardiogram with available estimates of pulmonary pressure and right ventricular function. Analyses of the study were performed between 2020 and 2022. The final analytical sample included 14 861 participants (mean [SD] age, 63 [15] years and mean [SD] body mass index, 29 [7] kg/m). An unbiased phenome-wide association study identified diabetes as the most statistically significant clinical , () code associated with polygenic risk for increased pulmonary pressure. We validated this finding further by finding significant associations between genetic risk for diabetes and a related condition, obesity, with pulmonary pressure estimate. We then used 2-sample univariable Mendelian randomization and multivariable Mendelian randomization to show that diabetes, but not obesity, was independently associated with genetic risk for increased pulmonary pressure and decreased right ventricle load stress. Conclusions Our findings show that genetic risk for diabetes is the only significant independent causative driver of genetic risk for increased pulmonary pressure and decreased right ventricle load stress. These findings suggest that therapies targeting genetic risk for diabetes may also potentially be beneficial in treating pulmonary hypertension and right heart dysfunction.
Topics: Humans; Middle Aged; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Heart Ventricles; Hypertension, Pulmonary; Obesity; Risk Factors; Aged
PubMed: 37522172
DOI: 10.1161/JAHA.122.029190