2018 Fiscal Year Final Research Report

Clarification of the mechanism of pulmonary arteriopathy associated with congenital heart diseases and development of new treatment using lung biopsy speciments

Research Project

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Project/Area Number	16K15627
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Cardiovascular surgery
Research Institution	Tohoku University
Principal Investigator	Saiki Yoshikatsu 東北大学, 医学系研究科, 教授 (50372298)
Co-Investigator(Kenkyū-buntansha)	川本俊輔東北大学, 医学系研究科, 非常勤講師 (20400244) 堀井明東北大学, 医学系研究科, 教授 (40249983) 遠藤雅人東北大学, 医学系研究科, 非常勤講師 (90282128) 齋木由利子東北大学, 医学系研究科, 准教授 (80311223)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	先天性心疾患 / 肺動脈性肺高血圧症 / 肺生検
Outline of Final Research Achievements	We demonstrated the following histopathological findings in the patients with pulmonary arterial hypertension (PAH) associated with congenital heart diseases (CHD) using lung biopsy specimens. Pulmonary artery banding can induce pulmonary vascular reverse remodeling as demonstrated by significant pulmonary artery medial thinning and improvement in intimal lesions. In addition, early progression of pulmonary arteriopathy in patients with trisomy 21 was not proved compared with patients without trisomy 21. Moreover, microthrombotic lesions were detected in 7% of patients with CHD and these lesions would be associated with the progression of PAH. We could not demonstrate the mechanisms of the PAH progression by the molecular biological methods using laser microdissection method and DNA microarray. We will perform further investigation and clarify novel mechanisms of the progression of PAH with CHD.
Free Research Field	心臓血管外科学分野
Academic Significance and Societal Importance of the Research Achievements	先天性心疾患に伴う肺動脈性肺高血圧症における肺血管病変の組織学的特徴が示されたことにより、各症例に応じより良い治療選択が可能になる可能性が示された。加えて肺血管拡張薬のみならず、呼吸器やその他に対するアプローチの必要性や、これまでにそれほど重要視されていなかった血栓性病変に対する新たなアプローチの可能性が示唆された。今後、免疫組織化学的手法等より肺血管病変進行のさらなるメカニズム解明が進めば、新たな治療標的として新薬開発にもつながることが期待できると考えている。