• Molecules and Cells
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• v.37 no.3
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• pp.196-201
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• 2014

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by the vascular remodeling of the pulmonary arterioles, including formation of plexiform and concentric lesions comprised of proliferative vascular cells. Clinically, PAH leads to increased pulmonary arterial pressure and subsequent right ventricular failure. Existing therapies have improved the outcome but mortality still remains exceedingly high. There is emerging evidence that the seven-transmembrane G-protein coupled receptor APJ and its cognate endogenous ligand apelin are important in the maintenance of pulmonary vascular homeostasis through the targeting of critical mediators, such as Kr$\ddot{u}$ppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and microRNAs (miRNAs). Disruption of this pathway plays a major part in the pathogenesis of PAH. Given its role in the maintenance of pulmonary vascular homeostasis, the apelin-APJ pathway is a potential target for PAH therapy. This review highlights the current state in the understanding of the apelin-APJ axis related to PAH and discusses the therapeutic potential of this signaling pathway as a novel paradigm of PAH therapy.

• BMB Reports
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• v.47 no.6
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• pp.311-317
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• 2014

microRNAs (miRNAs) are a class of small, non-coding RNAs that play critical posttranscriptional regulatory roles typically through targeting of the 3'-untranslated region of messenger RNA (mRNA). Mature miRNAs are known to be involved in global cellular processes, such as differentiation, proliferation, apoptosis, and organogenesis, due to their capacity to target multiple mRNAs. Thus, imbalances in the expression and/or activity of miRNAs are involved in the pathogenesis of numerous diseases, including pulmonary arterial hypertension (PAH). PAH is a progressive disease characterized by vascular remodeling due to excessive proliferation of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). Recently, studies have evaluated the roles of miRNAs involved in the pathogenesis of PAH in these pulmonary vascular cells. This review provides an overview of recent discoveries on the role of miRNAs in the pathogenesis of PAH and discusses the potential for miRNAs as therapeutic targets and biomarkers of PAH.

• Tuberculosis and Respiratory Diseases
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• v.67 no.3
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• pp.177-182
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• 2009

Pulmonary arterial hypertension is a progressive, symptomatic, and ultimately fatal disorder for which substantial advances in treatment have been made during the past decade. This article reviews the recent advances in the field of pulmonary arterial hypertension (PAH). Epidemiology, genetics, treatment and prognosis will be the main focus of this update.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.641-647
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• 2016

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats. Using hematoxylin and eosin staining, we confirmed vascular remodeling (i.e., medial thickening of PA) and right ventricle hypertrophy in PAH-MCT rats. The basal pulmonary arterial pressure (PAP) and PAP increase by a raised flow rate (40 mL/min) were higher in the PAH-MCT than in the control rats. In addition, both high $K^+$ (40 mM KCl)- and angiotensin II-induced PAP increases were higher in the PAH-MCT than in the control rats. Surprisingly, application of a nitric oxide synthase inhibitor, L-$N^G$-Nitroarginine methyl ester (L-NAME), induced a marked PAP increase in the PAH-MCT rats, suggesting that endothelial functions were recovered in the three-week PAH-MCT rats. In addition, the medial thickening of the PA was similar to that in chronic hypoxia-induced PAH (PAH-CH) rats. However, the HPV response (i.e., PAP increased by acute hypoxia) was not affected in the MCT rats, whereas HPV disappeared in the PAH-CH rats. These results showed that vascular contractility and HPV remain robust in the MCT-induced PAH rat model with vascular remodeling.

• Korean Circulation Journal
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• v.52 no.2
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• pp.110-122
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• 2022

Pulmonary hypertension is a rare and progressive illness with a devastating prognosis. Promising research efforts have advanced the understanding and recognition of the pathobiology of pulmonary hypertension. Despite remarkable achievements in terms of improving the survival rate, reducing disease progression, and enhancing quality of life, pulmonary arterial hypertension (PAH) is not completely curable. Therefore, an effective treatment strategy is still needed. Recently, many studies of the underlying molecular mechanisms and technological developments have led to new approaches and paradigms for PAH treatment. Management based on stem cells and related paracrine effects, epigenetic drugs and gene therapies has yielded prospective results for PAH treatment in preclinical research. Further trials are ongoing to optimize these important insights into clinical circumstances.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.142-150
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• 2006

Pulmonary arterial hypertension (PAH) is often difficult to diagnose and challenging to treat. Untreated, it is characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. The past decade has seen remarkable improvements in therapy, driven largely by the conduct of randomized controlled trials. Still, the selection of most appropriate therapy is complex, and requires familiarity with the disease process, evidence from treatment trials, complicated drug delivery systems, dosing regimens, side effects, and complications. We tried to provide evidence-based treatment recommendations for physicians involved in the care of these complex patients. Due to the complexity of the diagnostic evaluation required, and the treatment options available, it is strongly recommended that consideration be given to referral of patients with PAH to a specialized center.

• YAKHAK HOEJI
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• v.54 no.2
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• pp.126-133
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• 2010

This study was conducted to analyze cost-utility of bosentan versus iloprost indicated for pulmonary arterial hypertension (PAH) in a Korean healthcare setting from a payer's perspective. We constructed a Markov model to estimate total costs and outcomes for 1-year time horizon in a hypothetical cohort of 50-year-old patients with PAH. Base analysis showed that bosentan resulted in KW 5.5 billions saving and 18 quality-adjusted life year (QALY) gains per 100 patients compared to iloprost. Bosentan as a dominant strategy was found to be robust through various sensitivity analyses.

• Journal of Chest Surgery
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• v.50 no.5
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• pp.378-381
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• 2017

Patients with an atrial septal defect (ASD) and severe pulmonary arterial hypertension (PAH) are considered ineligible for defect closure surgery because of the risk of right ventricular decompensation and death after the operation. We report the case of a patient with large ASD and severe PAH who was able to undergo defect closure surgery successfully following long-term use of combined oral sildenafil and beraprost.

• Korean Journal of Radiology
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• v.20 no.6
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• pp.976-984
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• 2019

Objective: To establish diagnostic criteria for pulmonary arterial hypertension (PAH) in children by using parameters obtained through noninvasive cardiac computed tomography (CCT). Materials and Methods: We retrospectively measured parameters from CCT images of children from a single institution in a multiple stepwise process. A total of 208 children with mean age of 10.5 years (range: 4 days-18.9 years) were assessed. The variables were classified into three groups: the great arteries; the ventricular walls; and the bilateral ventricular cavities. The relationship between the parameters obtained from the CCT images and mean pulmonary arterial pressure (mPAP) was tested and adjusted by the children's body size. Reference curves for the pulmonary trunk diameter (PTD) and ratio of diameter of pulmonary trunk to ascending aorta (rPTAo) of children with CCT images of normal hearts, adjusted for height, were plotted. Threshold lines were established on the reference curves. Results: PTD and rPTAo on the CCT images were significantly positively correlated with mPAP (r > 0.85, p < 0.01). Height was the body size parameter most correlated with PTD (r = 0.91, p < 0.01) and rPTAo (r = -0.69, p < 0.01). On the basis of the threshold lines on the reference curves, PTD and rPTAo both showed 88.9% sensitivity for PAH diagnosis, with negative predictive values of 93.3% and 92.9%, respectively. Conclusion: PTD and rPTAo measured from CCT images were significantly correlated with mPAP in children. Reference curves and the formula of PTD and rPTAo adjusted for height could be practical for diagnosing PAH in children.

• International Journal of Stem Cells
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• v.15 no.2
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• pp.122-135
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• 2022

Background and Objectives: Endothelial progenitor cells (EPCs) and endothelial cells (ECs) have been applied in the clinic to treat pulmonary arterial hypertension (PAH), a disease characterized by disordered pulmonary vasculature. However, the lack of sufficient transplantable cells before the deterioration of disease condition is a current limitation to apply cell therapy in patients. It is necessary to differentiate pluripotent stem cells (PSCs) into EPCs and identify their characteristics. Methods and Results: Comparing previously reported methods of human PSCs-derived ECs, we optimized a highly efficient differentiation protocol to obtain cells that match the phenotype of isolated EPCs from healthy donors. The protocol is compatible with chemically defined medium (CDM), it could produce a large number of clinically applicable cells with low cost. Moreover, we also found PSCs-derived EPCs express CD133, have some characteristics of mesenchymal stem cells and are capable of homing to repair blood vessels in zebrafish xenograft assays. In addition, we further revealed that IPAH PSCs-derived EPCs have higher expression of proliferation-related genes and lower expression of immune-related genes than normal EPCs and PSCs-derived EPCs through microarray analysis. Conclusions: In conclusion, we optimized a highly efficient differentiation protocol to obtain PSCs-derived EPCs with the phenotypic and molecular characteristics of EPCs from healthy donors which distinguished them from EPCs from PAH.