Faculty Profiles - akihide Tanimoto

Ka-ichiro Takeishi, Masahisa Horiuchi, Hiroaki Kawaguchi, Yoshiki Deguchi, Hiroyuki Izumi, Emi Arimura, Satoshi Kuchiiwa, Akihide Tanimoto, Toru Takeuchi . Acupuncture Improves Sleep Conditions of Minipigs Representing Diurnal Animals through an Anatomically Similar Point to the Acupoint (GV20) Effective for Humans . EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE2012 472982 - 472982 2012Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：HINDAWI LTD

Acupuncture, an alternative medicine, has been widely applied for people with sleep disturbances; therefore, the effects should be evaluated objectively. Micro-minipigs (MMPigs), the smallest miniature pigs for animal experiments, were used. Acupuncture was performed at two different points: Dafengmen is located on the head and is an anatomically similar point to human-Baihui (GV20), an effective acupoint for sleep disturbances in humans; pig-Baihui is on the back. The procedure was performed as follows: shallow, within 5 mm depth for several seconds; deep, 10-20 mm depth for 20 min. The sleep conditions were evaluated by actigraph, and the amount of catecholamine in pooled urine after acupuncture treatment. MMPigs with deep acupuncture at Dafengmen showed significantly efficient values on actigraph and catecholamine analysis as compared with untreated MMPigs. The effective acupoint for sleep conditions in the porcine model is at an anatomically similar point to humans, rather than the point determined by traditional Chinese medicine.

DOI： 10.1155/2012/472982

Yasuyo Ohi, Yoshihisa Umekita, Takako Yoshioka, Masakazu Souda, Yoshiaki Rai, Yoshiaki Sagara, Yasuaki Sagara, Yoshiatsu Sagara, Akihide Tanimoto . Aldehyde dehydrogenase 1 expression predicts poor prognosis in triple-negative breast cancer . HISTOPATHOLOGY59 ( 4 ) 776 - 780 2011.10Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Aims: Aldehyde dehydrogenase 1 (ALDH1) has been identified as a reliable marker of breast cancer stem cells, and its clinical significance as a prognostic indicator of breast cancer has been reported by several investigators. However, the clinical significance of ALDH1 expression in triple-negative (TN) breast cancer, a high-risk breast cancer lacking the benefit of specific therapy, remains to be solved.
Methods and results: We performed immunohistochemical analyses of 106 TN breast cancers, using paraffin-embedded sections. The basal-like phenotype was also investigated with the use of basal cytokeratin 5/6 and epidermal growth factor receptor. ALDH1 expression in carcinoma cells was found in 59% of cases and was correlated with high histological grade alone (P < 0.006), whereas ALDH1 expression in stromal cells was found in 49% of cases but was not correlated with any clinicopathological parameter. Patients with ALDH1 expression in carcinoma cells had a shorter relapse-free survival (RFS) according to the log-rank test (P = 0.015). According to Cox multivariate analysis, ALDH1 expression in carcinoma cells was an independent prognostic indicator of RFS (P = 0.025). The log-rank test revealed that stromal expression of ALDH1 had no effect on RFS.
Conclusions: ALDH1 expression in carcinoma cells is an independent prognostic factor in TN breast cancer patients.

DOI： 10.1111/j.1365-2559.2011.03884.x

Yumi Furuno, Tsuyoshi Morishita, Yumiko Toyohira, Sohsuke Yamada, Susumu Ueno, Naoya Morisada, Kazunari Sugita, Katsuhiko Noguchi, Mayuko Sakanashi, Hironori Miyata, Akihide Tanimoto, Yasuyuki Sasaguri, Hiroaki Shimokawa, Yutaka Otsuji, Nobuyuki Yanagihara, Masahito Tamura, Masato Tsutsui . Crucial vasculoprotective role of the whole nitric oxide synthase system in vascular lesion formation in mice: Involvement of bone marrow-derived cells . NITRIC OXIDE-BIOLOGY AND CHEMISTRY25 ( 3 ) 350 - 359 2011.10Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Although all three nitric oxide (NO) synthases (nNOS, iNOS, and eNOS) are expressed in injured arteries, it remains to be elucidated the role of the NOSs in their entirety in the vascular lesion formation. We addressed this issue in mice deficient in all NOS genes. Vascular injury was induced by permanent ligation of a unilateral carotid artery in wild-type (WT), singly, and triply NOS(-/-) mice. Two weeks after the procedure, constrictive vascular remodeling and neointimal formation were recognized in the ligated arteries. While constrictive remodeling was noted in the nNOS(-/-) and iNOS(-/-) genotypes, it was most accelerated in the nfi/eNOS(-/-) genotype. While neointimal formation was evident in the eNOS(-/-) and nNOS(-/-) genotypes, it was also most aggravated in the n/i/eNOS(-/-) genotype. Those lesions were reversed by long-term treatment with isosorbide dinitrate, a NO donor. Finally, we examined the involvement of bone marrow-derived cells in the vascular lesion formation. Bone marrow from the WT, singly, or triply NOS(-/-) mice was transplanted into the WT mice, and then the carotid ligation was performed. Intriguingly, constrictive remodeling and neointimal formation were both similarly most exacerbated in the case of the n/i/eNOS(-/-) bone marrow transplantation. These results indicate that the complete disruption of all the NOS genes causes markedly accelerated vascular lesion formation caused by blood flow disruption in mice in vivo, demonstrating the crucial vasculoprotective role of the whole endogenous NOS system. Our findings also suggest that the NOS system in bone marrow-derived cells may be involved in this vasculoprotective mechanism. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.niox.2011.06.007

Yoshihisa Umekita, Masakazu Souda, Kazuhito Hatanaka, Taiji Hamada, Takako Yoshioka, Hiroaki Kawaguchi, Akihide Tanimoto . Gene expression profile of terminal end buds in rat mammary glands exposed to diethylstilbestrol in neonatal period . TOXICOLOGY LETTERS205 ( 1 ) 15 - 25 2011.8Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Diethlstilbestrol (DES) is a synthetic estrogen prescribed to several millions of pregnant women worldwide. The risk for breast cancer after age 40 in women prenatally exposed to DES has been reported; however, the precise mechanism of susceptibility to breast cancer remains to be resolved. We investigated the global gene expression profile of terminal end buds (TEBs), the target of carcinogen, in rat mammary glands neonatally exposed to a low- or high-dose DES at postnatal days (PND) 35 and 45, equivalent to the peripubertal stage in humans. In all groups, the number of TEBs gradually increased, peaked at PND35 and decreased at PND49. At PND35 and 49, the low-dose DES-treated group (low-DES group) showed the highest number of TEBs. In the low-DES group at PND35, beta-casein, gamma-casein and whey acidic protein (WAP) mRNA expression increased 8.2-fold, 26.1-fold and 13.3-fold, respectively, whereas gamma-casein and WAP mRNA decreased 17.6-fold and 27.7-fold, respectively, at PND49. The most significant network revealed by Ingenuity Pathway Analysis (IPA) software showed the relevance of NF-kappa B in low-DES group. The present findings suggest that the deregulation of mammary gland differentiation and development-related genes could be induced and cause the increased number of terminal duct lobular units (TDLUs) in human mammary glands of DES daughters in a critical period of mammary gland development. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.toxlet.2011.04.031

Sohsuke Yamada, Yan Ding, Akihide Tanimoto, Ke-Yong Wang, Xin Guo, Zhi Li, Takashi Tasaki, Atsunori Nabesima, Yoshitaka Murata, Shohei Shimajiri, Kimitoshi Kohno, Hidenori Ichijo, Yasuyuki Sasaguri . Apoptosis Signal-Regulating Kinase 1 Deficiency Accelerates Hyperlipidemia-Induced Atheromatous Plaques via Suppression of Macrophage Apoptosis . ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY31 ( 7 ) 1555 - U172 2011.7Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Objective-The pathogenic role of macrophage apoptosis in atherosclerosis is still debatable, but it is considered to be a suppressor of plaque progression in early stages but a promoter of plaque necrosis in advanced stages. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays a pivotal role in stress-induced apoptosis. In the current study, we investigated the functions of ASK1 in hyperlipidemia-induced atherosclerosis.
Methods and Results-We generated ASK1 and apolipoprotein E (apoE) double-knockout mice (ASK1(-/-)/apoE(-/-)) and analyzed atherosclerosis in ASK1(-/-)/apoE(-/-) mice fed a high-cholesterol diet for 12 weeks. ASK1(-/-)/apoE(-/-) mice had accelerated hyperlipidemia-induced atherosclerosis, which was characterized by less apoptosis of macrophages and fewer necrotic areas, and more macrophages and elastolysis compared with apoE(-/-) mice. Bone marrow transplantation from ASK1(-/-) or wild-type to apoE(-/-) mice confirmed the above observation that the recipient mice of ASK1(-/-) donors had more pronounced hyperlipidemia-induced atherosclerosis than recipient mice of wild-type donors.
Conclusion-These findings suggest that ASK1 suppresses hyperlipidemia-induced atherosclerosis via increased macrophage apoptosis and that ASK1 may cause pronounced plaque vulnerability via necrotic core development. (Arterioscler Thromb Vasc Biol. 2011; 31:1555-1564.)

DOI： 10.1161/ATVBAHA.111.227140

Masahiro Yokouchi, Mikio Terahara, Satoshi Nagano, Yoshiya Arishima, Michihisa Zemmyo, Takako Yoshioka, Akihide Tanimoto, Setsuro Komiya . Clinical implications of determination of safe surgical margins by using a combination of CT and 18FDG-positron emission tomography in soft tissue sarcoma . BMC MUSCULOSKELETAL DISORDERS12 166 - 166 2011.7Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: To determine safe surgical margins for soft tissue sarcoma, it is essential to perform a general evaluation of the extent of tumor, responses to auxiliary therapy, and other factors preoperatively using multiple types of diagnostic imaging. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is a tool for diagnostic imaging that has recently spread rapidly in clinical use. At present, the roles played by FDG-PET/CT in determination of margins for surgical resection of sarcoma are unclear. The present study was undertaken to explore the roles of FDG-PET/CT in determination of surgical margins for soft tissue sarcoma and to examine whether PET can serve as a standard means for setting the margins of surgical resection during reduced surgery.
Methods: The study involved 7 patients with sarcoma who underwent surgery in our department and in whom evaluation with FDG-PET/CT was possible. Sarcoma was histologically rated as MFH in 6 cases and leiomyosarcoma in 1 case. In all cases, sarcoma was superficial (T1a or T2a). The tumor border was defined by contrast-enhanced MRI, and SUVs were measured at intervals of 1 cm over a 5-cm long area from the tumor border. Mapping of viable tumor cells was carried out on whole-mount sections of resected tissue, and SUVs were compared with histopathological findings.
Results: Preoperative maximum SUVs (SUV-max) of the tumor averaged 11.7 (range: 3.8-22.1). Mean SUV-max was 2.2 (range: 0.3-3.8) at 1 cm from the tumor border, 1.1 (0.85-1.47) at 2 cm, 0.83 (0.65-1.15) at 3 cm, 0.7 (0.42-0.95) at 4 cm, and 0.64 (0.45-0.82) at 5 cm. When resected tissue was mapped, tumor cells were absent in the areas where SUV-max was below 1.0.
Conclusions: Our findings suggest that a safe surgical margin free of viable tumor cells can be ensured if the SUV cut-off level is set at 1.0. FDG-PET/CT is promising as a diagnostic imaging technique for setting of safe minimal margins for surgical resection of soft tissue sarcoma.

DOI： 10.1186/1471-2474-12-166

Ke-Yong Wang, Akihide Tanimoto, Xin Guo, Sohsuke Yamada, Shohei Shimajiri, Yoshitaka Murata, Yan Ding, Masato Tsutsui, Seiya Kato, Teruo Watanabe, Hiroshi Ohtsu, Ken-Ichi Hirano, Kimitoshi Kohno, Yasuyuki Sasaguri . Histamine Deficiency Decreases Atherosclerosis and Inflammatory Response in Apolipoprotein E Knockout Mice Independently of Serum Cholesterol Level . ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY31 ( 4 ) 800 - U188 2011.4Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Objective-Histamine and histamine receptors are found in atherosclerotic lesions, and their signaling and subsequent proatherogenic or proinflammatory gene expression are involved in atherogenesis. In the present study, we generated apolipoprotein E (apoE) and histamine synthesizing histidine decarboxylase double knockout (DKO) mice on a C57BL/6J (wild-type mice) background to clarify the roles of histamine in atherosclerosis.
Methods and Results-Wild-type, apoE knockout (KO), and DKO mice were fed a high-cholesterol diet to analyze hyperlipidemia-induced atherosclerosis. Compared with wild-type mice, apoE-KO mice showed increased expression of histamine and its receptors, corresponding to increased atherosclerotic lesion areas and expression of inflammatory regulators, such as nuclear factor-kappa B, scavenger receptors, inflammatory cytokines, and matrix metalloproteinases. Histamine deficiency after deletion of histidine decarboxylase reduced atherosclerotic areas and expression of a range of the inflammation regulatory genes, but serum cholesterol levels of DKO mice were higher than those of apoE-KO mice.
Conclusion-These results indicate that histamine is involved in the development of atherosclerosis in apoE-KO mice by regulating gene expression of inflammatory modulators, an action that appears to be independent of serum cholesterol levels. In addition to acute inflammatory response, histamine participates in chronic inflammation, such as hyperlipidemia-induced atherosclerosis, and might be a novel therapeutic target for the treatment of atherosclerosis. (Arterioscler Thromb Vasc Biol. 2011;31:800-807.)

DOI： 10.1161/ATVBAHA.110.215228

Bin Han, Hiroto Izumi, Yoshihiro Yasuniwa, Masaki Akiyama, Takahiro Yamaguchi, Naohiro Fujimoto, Tetsuro Matsumoto, Bin Wu, Akihide Tanimoto, Yasuyuki Sasaguri, Kimitoshi Kohno . Human mitochondrial transcription factor A functions in both nuclei and mitochondria and regulates cancer cell growth . BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS408 ( 1 ) 45 - 51 2011.4Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Mitochondrial transcription factor A (mtTFA) is one of the high mobility group protein family and is required for both transcription from and maintenance of mitochondrial genomes. However, the roles of mtTFA have not been extensively studied in cancer cells. Here, we firstly reported the nuclear localization of mtTFA. The proportion of nuclear-localized mtTFA varied among different cancer cells. Some mtTFA binds tightly to the nuclear chromatin. DNA microarray and chromatin immunoprecipitation assays showed that mtTFA can regulate the expression of nuclear genes. Overexpression of mtTFA enhanced the growth of cancer cell lines, whereas downregulation of mtTFA inhibited their growth by regulating mtTFA target genes, such as baculoviral IAP repeat-containing 5 (BIRC5; also known as survivin). Knockdown of mtTFA expression induced p21-dependent G1 cell cycle arrest. These results imply that mtTFA functions in both nuclei and mitochondria to promote cell growth. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2011.03.114

畑中一仁, 吉岡孝子, 梅北善久, 谷本昭英 . 診断に苦慮した細気管支肺胞上皮癌の1例 . 診断病理28 ( 2 ) 126 - 129 2011.4

Publisher：(一社)日本病理学会

70代、女性。乳癌術後、右下葉に増大傾向のあるmixed-ground glass opacity陰影を認め、区域切除術を施行。組織学的には構造が保たれた肺胞上皮置換性の病変で、異型は弱く、粘液貯留や線毛を有する細胞が混在した複雑な像を認めた。免疫染色より転移は否定的で、粘液非産生性の単一な細胞の肺胞上皮置換性増殖より粘液非産生性細気管支肺胞上皮癌と診断した。粘液や線毛上皮の混在は背景の間質性変化に伴うものと考えられた。近年、末梢小型腺癌を診断する機会が増えているが、本症例のように異型が弱く、背景に間質性変化等が加わった複雑な像の場合には標本全体像の把握が重要である。(著者抄録)

Yoshihisa Umekita, Yasuyo Ohi, Masakazu Souda, Yoshiaki Rai, Yoshiaki Sagara, Yasuaki Sagara, Shugo Tamada, Akihide Tanimoto . Maspin expression is frequent and correlates with basal markers in triple-negative breast cancer . DIAGNOSTIC PATHOLOGY6 36 - 36 2011.4Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Maspin is a unique member of the serine protease inhibitor superfamily and its expression is found in myoepithelial cells of normal mammary glands; therefore, it has been considered to be a myoepithelial marker. We previously reported that maspin was frequently expressed in biologically aggressive breast cancers. In turn, triple-negative (TN) breast cancer is a subtype of tumor with aggressive clinical behavior and shows frequent expression of basal markers. We hypothesized that maspin expression may be frequent and correlate with basal rather than myoepithelial markers in TN breast cancer.
Methods: Paraffin-embedded 135 TN invasive ductal carcinoma tissue samples were immunohistochemically investigated using the Dako Envision+ kit and primary antibodies for maspin, basal (CK5/6, EGFR, CK14) and myoepithelial markers (p63, CD10). The correlation between maspin expression and relapse-free survival (RFS) was investigated by the log-rank test.
Results: The positive rate for maspin was 85.9% and significantly correlated with younger age (P = 0.0015), higher histological grade (P = 0.0013), CK5/6 positivity (P < 0.0001), CK14 positivity (P = 0.0034) and the basal-like subtype defined by CK5/6, EGFR and CK14 positivity (P = 0.013). The positive rates for CK5/6, EGFR, CK14, CD10 and p63 were 59.2%, 48.9%, 34.1%, 17.8% and 12.6%, respectively. There was no significant correlation between maspin expression and RFS.
Conclusions: The positive rate for maspin is the highest among known basal and myoepithelial markers, and strongly correlates with basal markers in TN breast cancer. These results suggested that maspin could be a candidate for a therapeutic target for TN breast cancer.

DOI： 10.1186/1746-1596-6-36

Yasuyo Ohi, Yoshihisa Umekita, Yoshiaki Rai, Yasuaki Sagara, Shinichi Baba, Shugo Tamada, Yoshiaki Sagara, Taeko Kukita, Takako Yoshioka, Kazuhito Hatanaka, Yoshiatsu Sagara, Akihide Tanimoto . Mucocele-like lesions of the breast: a long-term follow-up study . DIAGNOSTIC PATHOLOGY6 29 - 29 2011.4Reviewed International journal

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Mucocele-like lesions (MLL) of the breast were originally described as benign lesions composed of multiple cysts lined by uniform flat to cuboidal epithelium with extravasated mucin, but subsequent reports described the coexistence of columnar cell lesions (CCL), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). Several reports have investigated whether core biopsy can diagnose MLL reliably; however, there is only one report with a long-term follow-up after excision of MLL. We report here 15 surgically excised MLL with a long-term follow-up.
Findings: Fifteen lesions diagnosed as MLL from 13 patients who had undergone excisional biopsy between January 2001 and December 2006 were retrieved and followed-up for 24-99 months (median 63.8). Two lesions were accompanied with CCL, 5 with ADH and 3 with low grade DCIS. Four lesions (2 ADH, 2 DCIS) were additionally resected and their histology revealed 2 ADH, one DCIS and one MLL with CCL. Of 4 lesions (3 ADH, one DCIS) without additional resection, one lesion (ADH) relapsed accompanied with DCIS at 37 months after excision.
Conclusions: MLL were frequently accompanied with CCL, ADH or low grade DCIS. Complete resection may be recommended in case of MLL with ADH or DCIS because of intralesional heterogeneity and the probabilities of relapse.

DOI： 10.1186/1746-1596-6-29

Takako Yoshioka, Yoshihisa Umekita, Yasuyo Ohi, Masakazu Souda, Yoshiatsu Sagara, Yasuaki Sagara, Yoshiaki Sagara, Yoshiaki Rai, Akihide Tanimoto . Aldehyde dehydrogenase 1 expression is a predictor of poor prognosis in node-positive breast cancers: a long-term follow-up study . HISTOPATHOLOGY58 ( 4 ) 608 - 616 2011.3Reviewed International journal

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Aims:
Aldehyde dehydrogenase 1 (ALDH1) has been identified as a reliable marker of breast cancer stem cells. The aim was to determine the prognostic significance of ALDH1 expression in a long-term follow-up study.
Methods and results:
Immunohistochemical analyses were performed on 257 invasive ductal carcinomas (IDCs), 109 matched lymph node metastases and 190 ductal carcinomas in situ (DCISs), using paraffin-embedded sections. ALDH1 expression was found in 26% of IDCs, and correlated with larger tumour size (P = 0.007), high histological grade (P < 0.001), HER2 overexpression (P < 0.001) and negative hormone receptor status (P < 0.001). ALDH1 expression was observed in 14% of DCISs but was not correlated with any clinicopathological parameter. The IDC patients were followed up for 7-190 months (median: 120 months), and groups with ALDH1 expression had shorter relapse-free survival (P = 0.0013) and overall survival (OS) (P = 0.0005) by log-rank test. By Cox's multivariate analysis, it had a weak effect on OS (P = 0.047), and its most significant effect on OS was observed in node-positive groups (P = 0.013). No significant differences in OS stratified by ALDH1 expression status in lymph node metastases were noted.
Conclusions:
ALDH1 expression in primary cancer is an independent prognostic factor in node-positive breast cancer patients.

DOI： 10.1111/j.1365-2559.2011.03781.x

Hiroaki Kawaguchi, Noriaki Miyoshi, Naoki Miura, Makoto Fujiki, Masahisa Horiuchi, Yasukatsu Izumi, Hiroaki Miyajima, Ryoichi Nagata, Kazuhiro Misumi, Toru Takeuchi, Akihide Tanimoto, Hiroki Yoshida . Microminipig, a Non-rodent Experimental Animal Optimized for Life Science Research: Novel Atherosclerosis Model Induced by High Fat and Cholesterol Diet . JOURNAL OF PHARMACOLOGICAL SCIENCES115 ( 2 ) 115 - 121 2011.2Reviewed

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE PHARMACOLOGICAL SOC

Atherosclerotic lesions were observed in male and ovariectomized female Microminipig (MMP) fed a high fat and cholesterol diet with sodium cholate (HFCD/SC) for 3 months. HFCD/SC induced hypercholesterolemia accompanied by an increase in serum total cholesterol (T-Cho), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and cholesterol ester (CE). Unlike the mouse or rabbit, a dominant LDL-C fraction in the intact M MP, similar to that in humans, was observed by serum lipoprotein analysis. HFCD/SC increased body weight gain. At the end of the experiment, computed tomography scans of conscious animals showed that HFCD/SC had decreased liver attenuation values (Hounsfield unit) and increased subcutaneous and abdominal fat, suggesting the induction of fatty liver and obesity. HFCD/SC induced atherosclerotic lesions in systemic arteries, including the external and internal iliac arteries, abdominal aorta, coronary artery, and cerebral arterial circle. Atherosclerosis and pathological findings induced by HFCD/SC in MMP were similar to those in humans. The MMP is a potentially suitable tool for investigating human atherosclerosis.

DOI： 10.1254/jphs.10R17FM