Increased plasma levels of big-endothelin-2 and big-endothelin-3 in patients with end-stage renal disease

LIFE SCIENCES

卷:91

Article; Proceedings Paper

Miyauchi, Yumi²  Sakai, Satoshi¹  Maeda, Seiji²  Shimojo, Nobutake¹  Watanabe, Shigeyuki¹  Honma, Satoshi¹  Kuga, Keisuke¹  Aonuma, Kazutaka¹  Miyauchi, Takashi^1,2 

[1] Univ Tsukuba, Fac Med, Div Clin Med, Dept Med Cardiol, Tsukuba, Ibaraki 3058575, Japan

[2] Univ Tsukuba, TARA, Life Sci Ctr, Tsukuba, Ibaraki 3058575, Japan

关键词: Endothelin;    Big endothelin;    Renal disease;    Hemodialysis patients;   

DOI  :  10.1016/j.lfs.2012.08.008

来源: Elsevier

【 摘 要 】

Aims: Big endothelins (pro-endothelin; inactive-precursor) are converted to biologically active endothelins (ETs). Mammals and humans produce three ET family members: ET-1, ET-2 and ET-3, from three different genes. Although ET-1 is produced by vascular endothelial cells, these cells do not produce ET-3, which is produced by neuronal cells and organs such as the thyroid, salivary gland and the kidney. In patients with end-stage renal disease, abnormal vascular endothelial cell function and elevated plasma ET-1 and big ET-1 levels have been reported. It is unknown whether big ET-2 and big ET-3 plasma levels are altered in these patients. The purpose of the present study was to determine whether endogenous ET-1. ET-2, and ET-3 systems including big ETs are altered in patients with end-stage renal disease. Main methods: We measured plasma levels of ET-1, ET-3 and big ET-1, big ET-2, and big ET-3 in patients on chronic hemodialysis (n = 23) and age-matched healthy subjects (n = 17). Key findings: In patients on hemodialysis, plasma levels (measured just before hemodialysis) of both ET-1 and ET-3 and big ET-1, big ET-2, and big ET-3 were markedly elevated, and the increase was higher for big ETs (Big ET-1, 4-fold; big ET-2, 6-fold; big ET-3: 5-fold) than for ETs (ET-1, 1.7-fold; ET-3, 2-fold). Significance: In hemodialysis patients, plasma levels of the inactive precursors big ET-1, big ET-2, and big ET-3 levels are markedly increased, yet there is only a moderate increase in plasma levels of the active products. ET-1 and ET-3. This suggests that the activity of endothelin converting enzyme contributing to circulating levels of ET-1 and ET-3 may be decreased in patients on chronic hemodialysis. (c) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

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