論文 - 魏 峻洸
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Gi T., Kuwahara A., Yamashita A., Matsuda S., Maekawa K., Moriguchi-Goto S., Sato Y., Asada Y.
Arteriosclerosis, thrombosis, and vascular biology 43 ( 1 ) 146 - 159 2023年1月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Arteriosclerosis, thrombosis, and vascular biology
BACKGROUND: Cancer-associated venous thromboembolism (VTE) is a critical complication in patients with cancer. However, the pathological findings of VTE are limited. Here, we investigated the histopathological features of cancer-associated VTE in human autopsy cases. METHODS: We clinically examined the autopsy cases of VTE with (n=114) and without cancer (n=66) and immunohistochemically analyzed the expression of prothrombotic factors in intrathrombus cancer cells, the thrombus contents of erythrocytes, fibrin, platelets, citrullinated histone H3, and degree of organization. RESULTS: Vascular wall invasion or small cell clusters of cancer cells was observed in thrombi in 27.5% of deep vein thrombosis and 25.9% of pulmonary embolism cases. The majority of the cancer cells in deep vein thrombi appeared to be invading the vessel wall, whereas the majority of pulmonary thrombi had cancer cell clusters, consistent with embolization via blood flow. These cancer cells were immunohistochemically positive for TF (tissue factors) or podoplanin in up to 88% of VTE cases. The frequency of TF-positive monocyte/macrophages in thrombi was higher in cancer-associated VTE than that in VTE without cancer. Citrullinated histone H3 was predominantly observed in the early stages of organizing thrombi. There was no significant difference in thrombus components between VTE with cancer and without cancer groups. CONCLUSIONS: Vascular wall invasion or cancer cell clusters in thrombi might influence thrombogenesis of cancer-associated VTE. TF and podoplanin in cancer cells and in monocyte/macrophages may induce coagulation reactions and platelet aggregation. Neutrophil extracellular traps may play a role in the early stages of VTE, regardless of cancer status.
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Nobuyuki Oguri, Toshihiro Gi, Eriko Nakamura, Kazunari Maekawa, Eiji Furukoji, Hoshimi Okawa, Sho Kouyama, Saki Horiuchi, Akira Sawaguchi, Tatefumi Sakae, Minako Azuma, Yujiro Asada, Atsushi Yamashita
Research and Practice in Thrombosis and Haemostasis 2025年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：ELSEVIER
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Histological differences among thrombi in thrombotic diseases. 招待あり 査読あり 国際誌
Yamashita A, Gi T, Sato Y
Current opinion in hematology 2025年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Lippincott
PURPOSE OF REVIEW: This review aims to summarize the histological differences among thrombi in acute myocardial infarction, ischemic stroke, venous thromboembolism, and amniotic fluid embolism, a newly identified thrombosis. RECENT FINDINGS: Acute coronary thrombi have a small size, are enriched in platelets and fibrin, and show the presence of fibrin and von Willebrand factor, but not collagen, at plaque rupture sites. Symptomatic deep vein thrombi are large and exhibit various phases of time-dependent histological changes. Cancer-associated venous thromboemboli contain invasive cancer cells that penetrate the vascular walls, and small cancer cell aggregates are observed within the thrombi. The thrombus composition in atherosclerotic and cardioembolic ischemic strokes varies from case to case, while the thrombi in cancer-associated ischemic stroke are rich in platelets and fibrin. A pathological study on amniotic fluid embolism identified uterine vein thrombi and massive platelet-rich microthrombi in the lungs. SUMMARY: Atherothrombus formation is induced by plaque disruption and may occlude a narrow lumen within a short time. Venous thrombi may grow to a large size in a multistage or chronic manner. Cancer cells can directly contribute to venous thrombus formation. The thrombus formation in amniotic fluid embolism may explain the occurrence of consumptive coagulopathy and cardiopulmonary collapse.
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Expression of fibroblast activation protein-α in human deep vein thrombosis 査読あり 国際誌
Oguri N., Gi T., Nakamura E., Furukoji E., Goto H., Maekawa K., Tsuji A.B., Nishii R., Aman M., Moriguchi-Goto S., Sakae T., Azuma M., Yamashita A.
Thrombosis Research 241 109075 2024年9月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Research
Background: Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT. Methods: We performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts. Results: All the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin. Conclusions: The heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity.
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Maekawa K., Nakamura E., Saito Y., Matsuura Y., Gi T., Nishihira K., Oguri N., Moriguchi-Goto S., Sato Y., Hatakeyama K., Shibata Y., Komohara Y., Kaikita K., Asada Y., Yamashita A.
PLoS ONE 20 ( 3 March ) e0316474 2025年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：PLoS ONE
Background The thrombogenic potential of cells within atherosclerotic plaques is critical in the formation of a coronary thrombus. We hypothesized that a combination of inflammatory and hypoxic stimuli enhances tissue factor (TF) expression and glycolysis in cells in atherosclerotic plaques and contributes to coronary thrombus formation. Aims To identify TF- and hexokinase (HK)-II-expressing cells in coronary atherosclerotic plaques and thrombi and determine the effects of combined inflammatory and hypoxic stimuli and glycolysis on TF expression in peripheral blood mononuclear cell-derived macrophages. Methods We immunohistochemically assessed TF and HK-II expression in stable (n = 20) and unstable (n = 24) human coronary plaques and aspirated acute coronary thrombi (n = 15). The macrophages were stimulated with tumor necrosis factor-α, interferon-γ, or interleukin-10 under normoxic (21% O2) or hypoxic (1% O2) conditions, and TF expression was assessed. Results TF and HK-II expression were increased in unstable plaques compared with stable plaques. The number of CD68- and HK-II-immunopositive cells positively correlated with the number of TF-immunopositive cells. TF- and HK-II-expressing macrophages, which expressed M1- or M2-like markers, were involved in platelet-fibrin thrombus formation in ruptured plaques. The combination of inflammatory and hypoxic conditions additively augmented TF expression and procoagulant activity in the cultured macrophages. Inhibition of glycolysis with 2-deoxyglucose reduced the augmented TF expression and procoagulant activity. Conclusion Combined inflammatory and hypoxic conditions in atherosclerotic plaques may markedly enhance procoagulant activity in macrophages and contribute to coronary thrombus formation following plaque disruption. Macrophage TF expression may be associated with glycolysis.
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僧帽弁形成術に関連した左室mesothelial/monocytic incidental cardiac excrescenceの一例 招待あり 査読あり
黒木麻由, 大栗伸行, 中村恵理子, 坂口修平, 魏 峻洸, 阿萬紫, 盛口淸香, 古川貢之, 佐藤勇一郎, 山下篤
診断病理 41 343 - 348 2024年12月
記述言語：日本語 掲載種別：症例報告
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Sugita C., Maekawa K., Gi T., Oguri N., Nakamura E., Furukoji E., Azuma M., Asada Y., Yamashita A.
Thrombosis Research 238 185 - 196 2024年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Research
Background: Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques. Aims: We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits. Methods and results: We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5′-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group. Conclusions: Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.
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Paratesticular cellular angiofibroma: a case report 査読あり 国際誌
Murashima T., Kida K., Gi T., Hida T., Fujii M., Nagai T., Takamori H., Mukai S., Sato Y., Kamoto T.
Journal of Medical Case Reports 18 ( 1 ) 170 2024年4月
記述言語：英語 掲載種別：症例報告 出版者・発行元：Journal of Medical Case Reports
Introduction: Paratesticular cellular angiofibroma is a rare benign mesenchymal tumor. The optimal management is surgical resection due to the difficulty of preoperative accurate diagnosis. Case presentation: A 51-year-old Japanese male visited our hospital complaining of asymptomatic left scrotal swelling. Physical examination revealed a nontender elastic paratesticular mass (5.5 cm in diameter). Although testicular germ cell tumor was ruled out clinically, the possibility of malignant potential remained for the tumor. Since the patient consented to complete resection, a transinguinal radical orchiectomy was performed. The pathological diagnosis revealed cellular angiofibroma. The patient recovered without perioperative complications, and no apparent recurrence was observed at 5 years after surgery. Conclusion: The pathological findings were compatible for cellular angiofibroma. The tumor was successfully resected, and no apparent recurrence was observed at 5 years after surgery.
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がん関連静脈血栓塞栓における血栓内がん細胞の存在 招待あり 査読あり
魏 峻洸
日本血栓止血学会誌 35 ( 4 ) 512 - 521 2024年
担当区分：筆頭著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本血栓止血学会
がん関連静脈血栓塞栓症（がん関連venous thromboembolism: VTE）は，担癌患者における致死的な病態の一つであるが，血栓部位の病理学的検討は極めて少ない．本研究ではVTEの剖検症例を用いて病理組織学的検討を行った．がん関連VTEでは，約3割の症例で血栓中にがん細胞を認め，血管周囲組織からの直接浸潤によるもの，あるいは小集簇性に存在していた．また，血栓内がん細胞の約4割に腫瘍壊死を認め，ダメージ関連分子パターン（DAMPs）放出が示唆された．免疫組織化学では，血栓内がん細胞には，組織因子あるいはポドプラニンの発現を約9割に認めた．これらの結果から，直接浸潤による血管壁の破壊や経血流的に侵入したがん細胞が組織因子，ポドプラニン，DAMPsを発現することで，凝固反応・血小板凝集を促進し，がん関連VTEの病態に直接的に寄与することが示唆された．
DOI： 10.2491/jjsth.35.512
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Yamashita A., Oda T., Aman M., Wakasa T., Gi T., Ide R., Todo Y., Tamura N., Sato Y., Itoh H., Asada Y.
BJOG: An International Journal of Obstetrics and Gynaecology 130 ( 13 ) 1685 - 1696 2023年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BJOG: An International Journal of Obstetrics and Gynaecology
Objective: To identify pulmonary/uterine thrombus formation in amniotic fluid embolism (AFE). Design: Retrospective, observational. Setting: Nationwide. Population: Eleven autopsy cases of AFE and control cases. Methods: We assessed pulmonary and uterine thrombus formation and thrombus area in AFE and pulmonary thromboembolism (PTE) as a control. The area of platelet glycoprotein IIb/IIIa, fibrin, neutrophil elastase, citrullinated histone H3 (a neutrophil extracellular trap marker) and mast cell chymase immunopositivity was measured in 90 pulmonary emboli, 15 uterine thrombi and 14 PTE. Main outcome measures: Pathological evidence of thrombus formation and its components in AFE. Results: Amniotic fluid embolism lung showed massive thrombus formation, with or without amniotic emboli in small pulmonary arteries and capillaries. The median pulmonary thrombus size in AFE (median, 0.012 mm2; P < 0.0001) was significantly smaller than that of uterine thrombus in AFE (0.61 mm2) or PTE (29 mm2). The median area of glycoprotein IIb/IIIa immunopositivity in pulmonary thrombi in AFE (39%; P < 0.01) was significantly larger than that of uterine thrombi in AFE (23%) and PTE (15%). The median area of fibrin (0%; P < 0.001) and citrullinated histone H3 (0%; P < 0.01) immunopositivity in pulmonary thrombi in AFE was significantly smaller than in uterine thrombi (fibrin: 26%; citrullinated histone H3: 1.1%) and PTE (fibrin: 42%; citrullinated histone H3: 0.4%). No mast cells were identified in pulmonary thrombi. Conclusions: Amniotic fluid may induce distinct thrombus formation in the uterus and lung. Pulmonary and uterine thrombi formation may contribute to cardiorespiratory collapse and/or consumptive coagulopathy in AFE.
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症例 ペムブロリズマブによる免疫関連有害事象と考えられたHypertrophic Lichen Planusの1例 招待あり
後田 優香, 西川 陽太郎, 野海 健太, 魏 峻洸, 天野 正宏
皮膚科の臨床 65 ( 12 ) 1896 - 1899 2023年11月
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Soejima H., Ogawa H., Morimoto T., Okada S., Matsumoto C., Nakayama M., Masuda I., Jinnouchi H., Waki M., Saito Y., Miwa K., Akahoshi K., Misumi K., Araki H., Mitsudo Y., Kondo N., Ashihara K., Yumoto S., Horimoto M., Doi O., Doijiri K., Fukami R., Shimabukuro M., Egusa G., Goto K., Hanaoka Y., Kimura Y., Haraguchi Y., Haraguchi O., Hasegawa A., Shioya Y., Shioya Y., Tanaka E., Yamada K., Atsumi T., Tanazawa S., Horio Y., Ichihara S., Yasuda I., Ikeda T., Ikemura M., Imamoto C., Iseri Y., Iwai K., Okamoto S., Sugiyama S., Kamura M., Kan H., Kiyota M., Kawamura K., Ono T., Koga T., Kinuwaki E., Naito H., Kozuma K., Kudou K., Morikami Y., Yasue H., Mizuno Y., Fujimoto H., Matsuyama K., Fujii H., Kamijikkoku S., Kuwahara T., Takaoka K., Machii K., Maeda K., Mahara K., Maki A., Manda N., Marutsuka K., Sameshima N., Gi T., Matsunaga T., Matsuo S., Okubo H., Minagawa F., Minoda K., Miyata J., Matsuo T., Momosaki S., Munakata T., Nakamura T., Nagano H., Goshi K., Sugimoto K., Naomi S., Nasu T., Tanaka H., Sonoda R., Kajiwara K., Odo T., Ogata H., Ogihara M., Ogura T., Oka K., Kawashima E., Oshima E., Ozaki K., Ozawa S.
Heart and Vessels 38 ( 11 ) 1371 - 1379 2023年11月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Heart and Vessels
Background: Dipeptidyl Peptidase-4 (DPP-4) inhibitors do not suppress cardiovascular events in diabetic patients with a history of cardiovascular disease. However, the effect of DPP-4 inhibitors on cardiovascular events in Japanese diabetic patients is unclear. Therefore, we investigated whether DPP-4 inhibitors alter the incidence of cardiovascular events in Japanese diabetic patients without a history of cardiovascular events. Methods: The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study conducted from 2002 to 2008. After completion of the JPAD trial, we followed up the patients until 2019. Patients who had had a cardiovascular event by the 2013 follow-up were excluded from the study. JPAD patients were divided into a DPP-4 group and a non-DPP-4 group based on whether they were taking DPP-4 inhibitors at the 2013 follow-up because few patients took DPP-4 inhibitors before 2013. We investigated the incidence of cardiovascular events consisting of coronary events, cerebrovascular events, heart failure requiring hospitalization, and aortic and peripheral vascular disease in 1099 JPAD patients until 2019. Results: During the observation period from 2013 to 2019, 37 (7%) first cardiovascular events occurred in the DPP-4 group (n = 518) and 66 (11%) in the non-DPP-4 group (n = 581). The incidence of cardiovascular events was significantly lower in the DPP-4 group than in the non-DPP-4 group (Log-Rank P = 0.0065). Cox proportional hazards model analysis revealed that the use of DPP-4 inhibitors (hazard ratio 0.65; 95% confidence interval 0.43–0.98; P = 0.038) was an independent factor after adjustment for age ≥ 65 years, hypertension, statin usage, and insulin usage. Conclusions: Our findings have demonstrated that the use of DPP-4 inhibitors may be associated with a reduced incidence of first cardiovascular events in Japanese diabetic patients. The results require confirmation in randomized controlled trials.
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Shimazu H., Matsuura Y., Moribayashi K., Gi T., Suiko Y., Tanaka H., Komaki S., Ishikawa T., Yamashita A., Kaikita K.
JACC: Case Reports 24 102017 2023年10月
記述言語：英語 掲載種別：症例報告 出版者・発行元：JACC: Case Reports
Immune thrombocytopenia (ITP) carries bleeding and thrombotic risks; however, thromboses associated with ITP have not been histologically examined. This report presents optical coherence tomography images of the culprit lesion and histology of coronary aspirates in very late stent thrombosis complicating severe ITP, providing evidence of platelet-rich thrombus formation. (Level of Difficulty: Advanced.)
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Magnetic Resonance Imaging of Cancer-Associated Deep Vein Thrombus in a Patient With Gastric Cancer. 査読あり 国際誌
Gi T, Kuroiwa Y, Kihara Y, Miyaushiro S, Yamashita A
Circulation reports 5 ( 6 ) 265 - 266 2023年6月
担当区分：筆頭著者 記述言語：英語 掲載種別：症例報告 出版者・発行元：一般社団法人 日本循環器学会
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症例報告 ボリコナゾール長期内服による多発有棘細胞癌の治療中に生じたMerkel細胞癌の1例 査読あり
森 愛菜, 持田 耕介, 西川 陽太郎, 中村 俊央, 魏 峻洸, 河野 徳明, 天野 正宏
臨床皮膚科 77 ( 6 ) 433 - 438 2023年5月
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ボリコナゾール長期内服による多発有棘細胞癌の治療中に生じたMerkel細胞癌の1例
森 愛菜, 持田 耕介, 西川 陽太郎, 中村 俊央, 魏 峻洸, 河野 徳明, 天野 正宏
臨床皮膚科 77 ( 6 ) 433 - 438 2023年5月
記述言語：日本語 掲載種別：症例報告 出版者・発行元：(株)医学書院
＜文献概要＞47歳,男性.11年前に急性骨髄性白血病に対して,同種骨髄移植および臍帯血移植を施行された.5年前より肺深在性真菌症に対してボリコナゾール(VRCZ)内服開始,その3年後に頭部に紅斑,びらん,4年後に多発有棘細胞癌(squamous cell carcinoma: SCC)を生じた.VRCZと紫外線の影響を考え内服中止し,イトラコナゾールへ変更した.多発するSCCは切除施行した.外来通院中に左頸部に1cm大の腫瘤が出現し,全摘生検施行し,Merkel細胞癌(Merkel cell carcinoma: MCC)と診断した.VRCZの長期投与と紫外線の影響はSCC発生のリスク因子と報告されているが,MCCを発症した報告は,医中誌やPubMedで検索した限り,自験例を除き1例しかない.さらに,VRCZの長期投与後にSCCとMCCが併発した症例は自験例以外に報告はなく,発症後はMCCの比較的急速な病勢の進行を認めることから,同様な病態では慎重な経過観察と早期の治療が必要である.
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肺気管支にSolitary fibrous tumorとIntercalated duct hyperplasiaの合併を認めた1例
佐藤 勇一郎, 黒木 将英, 前田 亮, 魏 峻洸, 山下 篤, 浅田 祐士郎
診断病理 40 ( 1 ) 96 - 100 2023年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：(一社)日本病理学会
Intercalated duct hyperplasia(IDH)は,唾液腺で提唱され,顕微鏡的に偶然発見される病変である。70歳代男性。今回肺切除術後の病理検体で,右上葉気管支壁にSolitary fibrous tumor(SFT)とともに最大径4mmの介在導管に類似した二相性の細胞からなる気管支腺の増生を認め,IDHと診断した。IDHはまれな病変で,これまで唾液腺以外の報告はなく,貴重な症例と思われた。(著者抄録)
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診断に難渋したUterine tumor resembling ovarian sex cord tumorの1例
佐藤 勇一郎, 魏 峻洸, 松澤 聡史, 藤崎 碧, 川越 靖之, 大西 淳仁, 桂木 真司
日本婦人科病理学会誌 13 ( 2 ) 73 - 76 2022年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本婦人科病理学会
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Intrapulmonary solitary fibrous tumor coexisting with lung adenocarcinomas. 査読あり 国際誌
Kuroki S, Ayabe T, Gi T, Sato Y, Nakada H, Maeda R
Surgical case reports 8 ( 1 ) 150 2022年8月
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Tomimori-Gi K, Katsuragi S, Kodama Y, Yamada N, Sameshima H, Maekawa K, Yamashita A, Gi T, Sato Y
Virchows Archiv 481 ( 5 ) 713 - 720 2022年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Virchows Archiv
Preeclampsia, a multisystem pregnancy-specific hypertensive disorder, results in significant maternal and perinatal morbidity and mortality. This condition is associated with placental histopathological abnormalities and particularly affects the decidual spiral arteries. Reportedly, aspirin prevents preeclampsia, specifically early-onset preeclampsia, although findings in decidual arteries in women treated with aspirin therapy remain unclear. We compared the clinical and histopathological placental findings between women with a history of preeclampsia, who did and did not receive low-dose aspirin therapy (LDA and non-LDA groups, respectively). We identified 26 women with a history of preeclampsia; 9 women received LDA (aspirin ≤ 100 mg/day, initiated at < 16 weeks, LDA group), and 17 women did not receive LDA (non-LDA group). The mean gestational age was higher (36.7 weeks vs. 32.3 weeks, P = 0.0221) and the incidence of preeclampsia was lower (11% vs. 59%, P = 0.0362) in the LDA than in the non-LDA group. Histopathologically, the incidence of decidual arteriopathy, particularly that of fibrinoid necrosis and thrombosis, was lower in the LDA than in the non-LDA group (44% vs. 88%, P = 0.0283). Immunohistologically, endothelial marker (CD31 and CD39) expression was stronger in the LDA than in the non-LDA group. Notably, we observed no significant intergroup differences in inflammatory changes (chronic perivasculitis, protease-activated receptor 1 expression, and CD3-positive cells). This study highlights that LDA inhibits hypertension-induced endothelial injury and thrombosis, and thereby protects maternal placental perfusion and prevents preeclampsia.