Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
kazunori Nakagawa Last modified date:2022.07.27

Lecturer / Pathobiology / Department of Basic Medicine / Faculty of Medical Sciences

1. Kazunori Nakagawa, Mitsuru Tanaka, Tae Hun Hahm, Huu-Nghi Nguyen, Toshiro Matsui, Yong-Xiang Chen, Yutaka Nakashima, Accumulation of Plasma-derived Lipids in the Lipid Core and Necrotic Core of Human Atheroma: Imaging Mass Spectrometry and Histopathological Analyses, Arteriosclerosis, Thrombosis, and Vascular Biology, doi: 10.1161/ATVBAHA.121.316154., 41, 11, e498-e511, Epub 2021 Sep 2., 2021.11.
2. Yokawa K, Hoshino M, Yagi N, Nakashima Y, Nakagawa K, Okita Y, Okada K, Tsukube T, Synchrotron Radiation-based X-ray Phase-Contrast Imaging of the Aortic Walls in Acute Aortic Dissection, The Journal of Vascular Surgery JVS - Vascular Science,, Available online 16 July 2020
[in press], 2020.07, Objective: Synchrotron radiation-based X-ray phase-contrast tomography imaging (XPCT) is an innovative modality for the quantitative analysis of three-dimensional morphology. This study used XPCT in order to evaluate the ascending aorta specimens from patients with acute type A aortic dissection (AADA) to analyze the morphological changes in the condition.
Methods: Twelve aortic specimens were obtained during repairs for AADA and fixed with formalin. Five specimens had Marfan syndrome (MFS), and seven did not have MFS. Six normal aortas were obtained from the autopsy. Using XPCT (effective pixel size, 12.5 μm), the density of the tunica media (TM) was measured at eight points for each sample. The specimens were subsequently analyzed pathologically.
Results: The density of the TM was almost constant within each normal aorta (mean ± standard deviation, 1.081 ± 0.001 g/cm3). The mean density was significantly lower for the formalin-fixed AADA aortas (1.066 ± 0.003 g/cm3; p < 0.0001), differing significantly between the intimal and adventitial sides (1.063 ± 0.003 vs. 1.074 ± 0.002 g/cm3, respectively; p < 0.0001). The overall density of the TM was significantly higher in the MFS aortas than in the other formalin-fixed AADA aortas (1.079 ± 0.008 g/cm3; p = 0.0003), with greater variation and markedly different distributions in comparison to that in the normal aortas. These density variations were consistent with the pathological findings, including the presence of cystic medial necrosis and malalignment of the elastic lamina in the AADA aortas with and without MFS.
Conclusion: XPCT demonstrated differences in the structure of the aortic wall in aortic dissection specimens with and without MFS and normal aortas. Medial density was homogeneous in the normal aortas, markedly varied in those with MFS, and was significantly lower and different among those without MFS. These changes would be presented in the TM before the onset of aortic dissection..
3. Kazunori Nakagawa, Yutaka Nakashima, Pathologic intimal thickening in human atherosclerosis is formed by extracellular accumulation of plasma-derived lipids and dispersion of intimal smooth muscle cells, Atherosclerosis, 10.1016/j.atherosclerosis.2018.03.039, 274, 235-242, 2018.07, Background and aims: Pathologic intimal thickening (PIT) is an important stage of atherosclerosis that leads to atheroma. The present study aimed to clarify the pathogenesis of PIT in humans. Methods: Coronary arteries were obtained from 43 autopsy subjects aged 15–49 years. Non-atherosclerotic intima and atherosclerotic intimal lesions were classified into four groups, i.e. diffuse intimal thickening, fatty infiltration, fatty streak, and PIT, and the number and density of macrophages and smooth muscle cells (SMCs) were determined. Components of the lesions and proliferative and apoptotic activities of macrophages and SMCs were investigated by immunohistochemistry and TUNEL assay. Results: Extracellular lipids accumulated mildly in the fatty infiltration and fatty streak, and abundantly in the PIT to form the lipid pool. The extracellular lipids co-localized with apolipoprotein B and fibrinogen. Macrophage foam cells accumulated in the fatty streak and PIT, but no TUNEL-positive macrophages were detected in any lesion. No significant difference in the number of SMCs was found between the four groups, but the density of SMCs decreased in the fatty streak and PIT. The decrease correlated with an increase in the number of macrophages, and the accumulation of extracellular lipids in the lipid pool. Neither Ki-67-positive nor TUNEL-positive SMCs were detected in any lesion. Conclusions: In PIT in human atherosclerosis, the lipid pool is formed by infiltration and deposition of plasma-derived lipids. Intimal SMCs are dispersed in association with macrophage infiltration and lipid pool formation without undergoing significant proliferation or death..
4. Tsukube T, Yagi N, Hoshino M, Nakashima Y, Nakagawa K, Okita Y, Impact of synchrotron radiation-based X-ray phase-contrast tomography on understanding various cardiovascular surgical pathologies., Gen Thorac Cardiovasc Surg, 10.1007/s11748-015-0565-4, 63, 10, 590-592, 2015.09, At SPring-8, synchrotron radiation-based X-ray phase-contrast tomography (PCXI) has been developed to measure the inner structures of biological soft tissue without destroying them. To resolve the three-dimensional (3D) morphology, we have applied PCXI to various cardiovascular tissue samples, including the thoracic aorta, ductus arteriosus, and cardiac conduction system. In the aortic walls, PCXI demonstrated differences in 3D structures of tunica media of aortic dissection. These findings correlated well with the irregularity of the structure of the media. In the surgically excised sample of coarctation of the aorta, PCXI showed 3D morphological changes in transition from the ductus arteriosus to the descending aorta. PCXI is also useful for examining abnormalities of the cardiac conduction system in congenital heart defects. Synchrotron radiation-based X-ray phase-contrast tomography has strong modality for analyzing 3D morphology and is useful for understanding the pathophysiology of various cardiovascular surgical pathologies..
5. Onimaru M, Yonemitsu Y, Fujii T, Tanii M, Nakano T, Nakagawa K, Kohno RI, Hasegawa M, Nishikawa SI, Sueishi K., VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B., Am J Physiol Heart Circ Physiol., [Epub ahead of print], 2009.09.
6. Murakami Y, Ikeda Y, Yonemitsu Y, Onimaru M, Nakagawa K, Kohno R, Miyazaki M, Hisatomi T, Nakamura M, Yabe T, Hasegawa M, Ishibashi T, Sueishi K., Inhibition of nuclear translocation of apoptosis-inducing factor is an essential mechanism of the neuroprotective activity of pigment epithelium-derived factor in a rat model of retinal degeneration., Am J Pathol., 173(5):1326-38., 2008.11.
7. Ikeda Y, Yonemitsu Y, Onimaru M, Nakano T, Miyazaki M, Kohno RI, Nakagawa K, Ueno A, Sueishi K, Ishibashi T., The regulation of vascular endothelial growth factors (VEGF-A, -C, and -D) expression in the retinal pigment epithelium., Exp Eye Res., 83(5):1031-1040.
, 2006.05.
8. Nagata S, Okano S, Yonemitsu Y, Yoshida K, Nagata H, Nakagawa K, Tomita Y, Yoshikai Y, Shimada M, Maehara Y, Sueishi K., The critical roles of memory T cells and anti-donor immunoglobulin in rejection of allogeneic bone marrow cells in sensitized recipient mice., Transplantation, 82(5):689-98., 2006.05.
9. Kuroda J, Nakagawa K, Yamasaki T, Nakamura K, Takeya R, Kuribayashi F, Imajoh-Ohmi S, Igarashi K, Shibata Y, Sueishi K, Sumimoto H., The superoxide-producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells., Genes to Cells, 10.1111/j.1365-2443.2005.00907.x, 10, 12, 1139-1151, 10(12):1139-51, 2005.12.
10. Shikada Y, Yonemitsu Y, Koga T, Onimaru M, Okano S, Sata S, Nakagawa K, Yoshino I, Maehara Y, Sueishi K., PDGF-AA is an essential and autocrine regulator of VEGF expression in non-small cell lung carcinomas., Cancer Research, 65(16):7241-8, 2005.01.
11. Sassa Y, Hata Y, Murata T, Yamanaka I, Honda M, Hisatomi T, Fujisawa K, Sakamoto T, Kubota T, Nakagawa K, Sueishi K, Ishibashi T., Functional role of Egr-1 mediating VEGF-induced tissue factor expression in the retinal capillary endothelium., Graefes Arch Clin Exp Ophthalmol, 10.1007/s00417-002-0576-6, 240, 12, 1003-1010, 240(12):1003-10, 2002.01.
12. Yamashita A, Yonemitsu Y, Okano S, Nakagawa K, Nakashima Y, Irisa T, Iwamoto Y, Nagai Y, Hasegawa M, Sueishi K, Fibroblast growth factor-2 determines severity of joint disease in adjuvant-induced arthritis in rats., J Immunol, 168, 1, 450-457, 168(1),pp450-457, 2002.01.
13. Masaki I, Yonemitsu Y, Komori K, Ueno H, Nakashima Y, Nakagawa K, Fukumura M, Kato A, Hasan M, Nagai Y, Sugimachi K, Alton EWFW, Hasegawa M, Sueishi K., Recombinant Sendai virus-mediated gene transfer to vasculature: a new class of efficient gene transfer vector to the vascular system., FASEB J, 15, 7, 1294-1296, 15(7): 1294-1296, 2001, 2001.01.
14. Ishibashi H, Shiratuchi T, Nakagawa K, Onimaru M, Sugiura T, Sueishi K, Shirasuna K, Hypoxia-induced angiogenesis of cultured human salivary gland carcinoma cells enhances vascular endothelial growth factor production and basic fibroblast growth factor release, Oral Oncology, 10.1016/S1368-8375(00)00062-2, 37, 1, 77-83, 37(1): 77-83, 2001.01.