Significance of BMPR2 mutations in pulmonary arterial hypertension |
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Authors: | Bintang Tatius Widya Wasityastuti Fajar Dwi Astarini Dwi Aris Agung Nugrahaningsih |
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Institution: | 1. Master in Biomedical Sciences, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, 55281, Indonesia;2. Biomedical Laboratory, Medicine Faculty, Universitas Muhammadiyah, Semarang, 50272, Indonesia;3. Department of Physiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia;4. Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia;1. Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan;2. Department of Respiratory Medicine and Allergology, Kindai University Nara Hospital, Ikoma, Nara 630-0293, Japan;1. Department of Respiratory Medicine, Kumamoto University Hospital, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan;2. Department of Pathology, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, 236-0051, Japan;3. Department of Thoracic Surgery, Kumamoto University Hospital, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan;1. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan;2. Department of Respiratory Medicine, Saitama Red Cross Hospital, Saitama, Japan;3. Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan |
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Abstract: | Pulmonary arterial hypertension (PAH) is a debilitating disease that results from progressive remodeling and inflammation of pulmonary arteries. PAH develops gradually, is difficult to diagnose, and has a high mortality rate. Although mutation in the bone morphogenetic protein receptor 2 (BMPR2) gene has been identified as the main genetic cause of PAH, the underlying pathways involving the pathophysiology of PAH are complex and still not fully understood. Endothelial dysfunction has been observed in PAH development that results in a multitude of disturbances in the cellular processes in pulmonary vessels. Changes in the pulmonary vasculature caused by the disruption of BMPR2 signaling are observed in three main vascular components; endothelial cells, smooth muscle cells, and fibroblasts. BMPR2 also has a prominent role in maintenance of the immune system. The disruption of BMPR2 signaling pathway causes an increased degree of inflammation and decreases the ability of the immune system to resolve it. Inflammatory processes and changes in pulmonary vasculature interact with one another, resulting in the progression of chronic PAH. In this review, we highlight the various components of vascular remodeling and immune response that are caused by disruption of BMPR2 signaling, including the clinical evidence and the prospects of these components as a potential target for PAH therapy. Indeed, development of drugs to target the pathogenic pathways involved in PAH may complement existing treatment regimens and improve patient prognosis. |
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Keywords: | Vascular remodeling Pulmonary arterial hypertension Inflammation |
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