著者

Hiroshi Kadowaki Junichi Ishida Hiroshi Akazawa Hiroki Yagi Akiko Saga-Kamo Masahiko Umei Ryo Matsuoka Qing Liu Hiroshi Matsunaga Hisataka Maki Yusuke Sato Haruki Kume Issei Komuro

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

pp.CR-21-0008, (Released:2021-03-10)

参考文献数

24

被引用文献数

6

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Background:Axitinib is a tyrosine kinase inhibitor (TKI) that inhibits vascular endothelial growth factor receptor signaling and is approved for second-line treatment of advanced renal cell carcinoma (RCC). Although the occurrence of hypertension with axitinib use has been documented, it is unclear whether a first-line TKI regimen can significantly affect the development of hypertension when axitinib is used as second-line therapy.Methods and Results:In this single-center retrospective study, advanced RCC patients treated with axitinib after first-line chemotherapy were divided into 2 groups according to the use of TKIs as part of first-line treatment before the initiation of axitinib. Clinical outcomes were compared between patients who were treated with (TKI(+); n=11) or without (TKI(–); n=11) a TKI. Although 63.6% of all patients had hypertension at baseline, axitinib-induced hypertension developed in 81.8% of patients, and 36.4% of patients experienced Grade 3 hypertension. After initiation of axitinib, both systolic and diastolic blood pressures and the hypertension grade were significantly elevated both in the TKI(+) and TKI(–) groups, and the number of antihypertensive drugs was significantly increased among all patients.Conclusions:This study suggests the need for proper monitoring and management of blood pressure in RCC patients treated with axitinib, regardless of a prior regimen with or without TKIs.

著者

Masahiko Umei Hiroshi Akazawa Akiko Saga-Kamo Hiroki Yagi Qing Liu Ryo Matsuoka Hiroshi Kadowaki Akito Shindo Ayaka Nakashima Kosuke Yasuda Kengo Suzuki Issei Komuro

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

vol.4, no.2, pp.83-91, 2022-02-10 (Released:2022-02-10)

参考文献数

40

被引用文献数

1

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Background:Patients with heart failure (HF) often experience gastrointestinal problems such as constipation, diarrhea, and disturbances to drug absorption. In HF, hypoperfusion and congestion cause structural and functional changes in the gut, which, in turn, lead to impaired cardiac function.Euglena gracilisZ (hereafter “Euglena”), calledMidorimushiin Japanese, is a microalga that is used as a food or nutritional supplement. It is unclear whether Euglena is beneficial for bowel habitus and cardiac function in subjects with HF.Methods and Results:We injected C57BL/6 male mice subcutaneously with isoproterenol (ISO) (20 mg/kg/day) for 7 days to examine bowel movement in HF. Euglena was orally administered to mice on anad libitum-feeding to a normal chow containing 2% dietary mixture. ISO induced a decrease in bowel movement and an increase in fecal retention in the cecum, as well as a decrease in left ventricular (LV) contraction. Euglena accelerated intestinal transit, relieved fecal retention, and prevented the alterations in gut pathology in ISO-treated mice. Euglena also suppressed ISO-induced decreases in LV contraction, although it had no significant effect on LV hypertrophy.Conclusions:The results suggested that oral administration of Euglena alleviated constipation and cardiac dysfunction in a mouse model of ISO-induced HF, and highlight the potential clinical benefit of Euglena in patients with HF in preventing constipation and contractile deterioration.

著者

Norifumi Takeda Hiroki Yagi Hironori Hara Takayuki Fujiwara Daishi Fujita Kan Nawata Ryo Inuzuka Yuki Taniguchi Mutsuo Harada Haruhiro Toko Hiroshi Akazawa Issei Komuro

出版者

一般社団法人 インターナショナル・ハート・ジャーナル刊行会

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

pp.16-094, (Released:2016-05-13)

被引用文献数

1 50

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Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue that affects the cardiovascular, skeletal, ocular, pulmonary, and nervous systems and is usually caused by mutations in the FBN1 gene, which encodes fibrillin-1. MFS is traditionally considered to result from the structural weakness of connective tissue. However, recent investigations on molecular mechanisms indicate that increased transforming growth factor-β (TGF-β) activity plays a crucial role in the pathogenesis of MFS and related disorders, such as Loeys–Dietz syndrome (LDS), which is caused by mutation in TGF-β signaling-related genes. In addition, recent studies show that angiotensin II type 1 receptor (AT1R) signaling enhances cardiovascular pathologies in MFS, and the angiotensin II receptor blocker losartan has the potential to inhibit aortic aneurysm formation. However, the relationship between TGF-β and AT1R signaling pathways remains poorly characterized. In this review, we discuss the recent studies on the molecular mechanisms underlying cardiovascular manifestations of MFS and LDS and the ensuing strategies for management.