Three-Dimensional Structure of Pulmonary Capillary Vessels in Patients With Pulmonary Hypertension
2010; Lippincott Williams & Wilkins; Volume: 121; Issue: 19 Linguagem: Inglês
10.1161/cir.0b013e3181e037c1
ISSN1524-4539
AutoresAya Miura, Kazufumi Nakamura, Kengo Kusano, Hiromi Matsubara, Aiko Ogawa, Satoshi Akagi, Takahiro Oto, Takuro MURAKAMI, Aiji Ohtsuka, Chikao Yutani, Tohru Ohe, Hiroshi Ito,
Tópico(s)Vascular Anomalies and Treatments
ResumoHomeCirculationVol. 121, No. 19Three-Dimensional Structure of Pulmonary Capillary Vessels in Patients With Pulmonary Hypertension Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBThree-Dimensional Structure of Pulmonary Capillary Vessels in Patients With Pulmonary Hypertension Aya Miura, MSc, Kazufumi Nakamura, MD, PhD, Kengo F. Kusano, MD, PhD, Hiromi Matsubara, MD, PhD, Aiko Ogawa, MD, PhD, Satoshi Akagi, MD, PhD, Takahiro Oto, MD, PhD, Takuro Murakami, MD, PhD, Aiji Ohtsuka, MD, PhD, Chikao Yutani, MD, PhD, Tohru Ohe, MD, PhD and Hiroshi Ito, MD, PhD Aya MiuraAya Miura From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. , Kazufumi NakamuraKazufumi Nakamura From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. , Kengo F. KusanoKengo F. Kusano From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. , Hiromi MatsubaraHiromi Matsubara From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. , Aiko OgawaAiko Ogawa From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. , Satoshi AkagiSatoshi Akagi From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. , Takahiro OtoTakahiro Oto From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. , Takuro MurakamiTakuro Murakami From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. , Aiji OhtsukaAiji Ohtsuka From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. , Chikao YutaniChikao Yutani From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. , Tohru OheTohru Ohe From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. and Hiroshi ItoHiroshi Ito From the Department of Cardiovascular Medicine (A.M., K.N., K.F.K., A. Ogawa, S.A., T. Ohe, H.I.), Department of Cancer and Thoracic Surgery (T. Oto), and Department of Human Morphology (T.M., A. Ohtsuka), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences; Division of Cardiology, National Hospital Organization, Okayama Medical Center (H.M.); and Department of Life Science (C.Y.), Okayama University of Science, Okayama, Japan. Originally published18 May 2010https://doi.org/10.1161/CIR.0b013e3181e037c1Circulation. 2010;121:2151–2153Pulmonary arterial hypertension, pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis are included in the same group (group 1) of clinical classification of pulmonary hypertension.1 Histological changes in the small pulmonary arteries (ie, intimal fibrosis and medial hypertrophy) are similar in these 3 diseases, and clinical presentations of the 3 diseases are often indistinguishable.1 However, it is estimated that the hemodynamics of capillary vessels are quite different in each disease. The hemodynamics of capillary vessels (ie, capillary occlusion) play an important role in cardiovascular diseases.2 Thus, clarification of the differences in the hemodynamics is essential to understand the pathophysiology of these 3 diseases.We obtained lung segments from patients with pulmonary hypertension who underwent living-donor lung transplantation and from patients with bronchogenic carcinoma who underwent lobectomy as described previously.3 All experiments were performed after approval was obtained from the Human Ethics Committee of Okayama University, and written informed consent was obtained from all patients before the procedure. We succeeded in visualization of the 3-dimensional structure of the pulmonary capillary in patients with pulmonary arterial hypertension, pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis using scanning electron microscopy of blood vascular casts.4A 42-year-old man underwent lobectomy for bronchogenic carcinoma. Figure 1A shows hematoxylin-eosin staining of a normal small pulmonary artery. Blood vascular architecture in the most distal area from the carcinoma in the resected lobe shows a normal capillary network around the alveolus of the lung (Figure 1B). Download figureDownload PowerPointFigure 1. Images of normal control microvessels. A, Hematoxylin-eosin staining of a small pulmonary artery (*). Bar=200 μm. B, Scanning electron micrograph of blood vascular casts. Bar=200 μm.A 20-year-old man underwent lung transplantation for idiopathic pulmonary arterial hypertension. The blood vascular architecture resembled dead branches. The small vessels were severely stenosed and were often occluded (Figure 2A), and the capillary was deficient (Figure 2B). Download figureDownload PowerPointFigure 2. Images of microvessels from a patient with pulmonary arterial hypertension. A, Hematoxylin-eosin staining of small pulmonary arteries (*). Bar=200 μm. B, Scanning electron micrograph of blood vascular casts. A deficient capillary network is seen. Bar=1 mm.A 27-year-old man underwent lung transplantation for pulmonary veno-occlusive disease. The small pulmonary veins were stenosed (Figure 3A), and capillary vessels were swollen compared with a normal capillary (Figure 3B). Download figureDownload PowerPointFigure 3. Images of microvessels from a patient with pulmonary veno-occlusive disease. A, Masson's trichrome staining of a small pulmonary vein (*). Bar=200 μm. B, Scanning electron micrograph of blood vascular casts. Swollen capillary vessels are seen. Bar=200 μm.A 14-year-old boy underwent lung transplantation for pulmonary capillary hemangiomatosis. A proliferation of capillaries was seen (Figure 4A), and the capillary vessels resembled a tumorous cluster (Figure 4B). Download figureDownload PowerPointFigure 4. Images of microvessels from pulmonary capillary hemangiomatosis. A, Hematoxylin-eosin staining of small pulmonary vessels. Bar=200 μm. B, Scanning electron micrograph of blood vascular casts. Tumorlike outgrowth of capillary vessels is seen. Bar=1 mm.Scanning electron microscopic study of blood vascular casts revealed the differences in the 3 diseases. Pulmonary arterial hypertension was characterized by a deficient capillary network, pulmonary veno-occlusive disease by swollen capillary vessels, and pulmonary capillary hemangiomatosis by a tumorlike outgrowth of capillaries. To the best of our knowledge, this is the first report on differences in the 3-dimensional structure of capillary vessels in normal controls, pulmonary arterial hypertension, pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis using scanning electron microscopy of blood vascular casts. These findings provide an insight into the basic mechanism responsible for pulmonary hypertension.*The first 2 authors contributed equally to this work.Sources of FundingThis work was supported by the Research Grant for Cardiovascular Diseases (19–9) from the Ministry of Health, Labour and Welfare, Japan.DisclosuresNone.FootnotesCorrespondence to Kazufumi Nakamura, MD, PhD, Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. E-mail [email protected]References1 Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing ZC, Krowka MJ, Langleben D, Nakanishi N, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009; 54: S43–S54.CrossrefMedlineGoogle Scholar2 Ito H. No-reflow phenomenon and prognosis in patients with acute myocardial infarction. Nat Clin Pract Cardiovasc Med. 2006; 3: 499–506.CrossrefMedlineGoogle Scholar3 Ogawa A, Nakamura K, Matsubara H, Fujio H, Ikeda T, Kobayashi K, Miyazaki I, Asanuma M, Miyaji K, Miura D, Kusano KF, Date H, Ohe T. Prednisolone inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Circulation. 2005; 112: 1806–1812.LinkGoogle Scholar4 Murakami T. Application of the scanning electron microscope to the study of the fine distribution of the blood vessels. Arch Histol Jpn. 1971; 32: 445–454.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Fu B, Jiang H, Che Y, Yang H and Luo Z (2020) Microanatomy of the lumbar vertebral bony endplate of rats using scanning electron microscopy, Orthopaedics & Traumatology: Surgery & Research, 10.1016/j.otsr.2019.12.026, 106:4, (731-734), Online publication date: 1-Jun-2020. Seki A, Anklesaria Z, Saggar R, Dodson M, Schwab K, Liu M, Charan Ashana D, Miller W, Vangala S, DerHovanessian A, Channick R, Shaikh F, Belperio J, Weigt S, Lynch J, Ross D, Sullivan L, Khanna D, Shapiro S, Sager J, Gargani L, Stanziola A, Bossone E, Schraufnagel D, Fishbein G, Xu H, Fishbein M, Wallace W and Saggar R (2019) Capillary Proliferation in Systemic‐Sclerosis‐Related Pulmonary Fibrosis: Association with Pulmonary Hypertension, ACR Open Rheumatology, 10.1002/acr2.1003, 1:1, (26-36), Online publication date: 1-Mar-2019. Schwaiger J, Loder C, Dobarro D, Kaier T, Reddecliffe S, Schreiber B, Handler C, Denton C and Coghlan J (2017) Optical coherence tomography evaluation of pulmonary arterial vasculopathy in Systemic Sclerosis, Scientific Reports, 10.1038/srep43304, 7:1, Online publication date: 1-Apr-2017. Horinouchi T, Mazaki Y, Terada K, Higashi T and Miwa S (2016) Current progress in therapeutic agents for pulmonary arterial hypertension: new insights into their mechanisms of action from endothelin system, Folia Pharmacologica Japonica, 10.1254/fpj.148.231, 148:5, (231-238), . Rea G, Valente T, de Rosa N, Muto M, Berritto D and Bocchino M (2015) Pulmonary Capillary Hemangiomatosis: A Diagnostic Challenge, Archivos de Bronconeumología (English Edition), 10.1016/j.arbr.2014.09.014, 51:2, (98-99), Online publication date: 1-Feb-2015. Rea G, Valente T, de Rosa N, Muto M, Berritto D and Bocchino M (2015) Hemangiomatosis capilar pulmonar: un reto diagnóstico, Archivos de Bronconeumología, 10.1016/j.arbres.2014.06.008, 51:2, (98-99), Online publication date: 1-Feb-2015. Akagi S, Nakamura K, Matsubara H, Ohta-Ogo K, Yutani C, Miyaji K, Ogawa A, Kusano K, Oto T, Ishibashi-Ueda H and Ito H (2014) Reverse remodeling of pulmonary arteries by high-dose prostaglandin I2 therapy: A case report, Journal of Cardiology Cases, 10.1016/j.jccase.2013.12.011, 9:5, (173-176), Online publication date: 1-May-2014. Nakamura K, Akagi S, Sarashina T, Ogawa A, Matsubara H and Ito H (2014) Treatment with imatinib for refractory PAH, Folia Pharmacologica Japonica, 10.1254/fpj.143.173, 143:4, (173-177), . Miura A, Akagi S, Nakamura K, Ohta-Ogo K, Hashimoto K, Nagase S, Kohno K, Kusano K, Ogawa A, Matsubara H, Toyooka S, Oto T, Ohtsuka A, Ohe T and Ito H (2013) Different sizes of centrilobular ground-glass opacities in chest high-resolution computed tomography of patients with pulmonary veno-occlusive disease and patients with pulmonary capillary hemangiomatosis, Cardiovascular Pathology, 10.1016/j.carpath.2012.12.002, 22:4, (287-293), Online publication date: 1-Jul-2013. 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Nakamura K, Sakaguchi M, Matsubara H, Akagi S, Sarashina T, Ejiri K, Akazawa K, Kondo M, Nakagawa K, Yoshida M, Miyoshi T, Ogo T, Oto T, Toyooka S, Higashimoto Y, Fukami K, Ito H and Ahmad S (2018) Crucial role of RAGE in inappropriate increase of smooth muscle cells from patients with pulmonary arterial hypertension, PLOS ONE, 10.1371/journal.pone.0203046, 13:9, (e0203046) Nakamura K, Matsubara H, Akagi S, Sarashina T, Ejiri K, Kawakita N, Yoshida M, Miyoshi T, Watanabe A, Nishii N and Ito H (2017) Nanoparticle-Mediated Drug Delivery System for Pulmonary Arterial Hypertension, Journal of Clinical Medicine, 10.3390/jcm6050048, 6:5, (48) Nakamura K, Akagi S, Ejiri K, Yoshida M, Miyoshi T, Toh N, Nakagawa K, Takaya Y, Matsubara H and Ito H (2019) Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension, International Journal of Molecular Sciences, 10.3390/ijms20235885, 20:23, (5885) May 18, 2010Vol 121, Issue 19 Advertisement Article InformationMetrics https://doi.org/10.1161/CIR.0b013e3181e037c1PMID: 20479166 Originally publishedMay 18, 2010 PDF download Advertisement SubjectsPulmonary Hypertension
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