Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin.
BACKGROUND
Urocortin, a neuropeptide discovered in the midbrain, is a member of the corticotropin-releasing factor family and is expressed in heart tissues. Urocortin exerts potent cardioprotective effects under various pathological conditions including ischemia/reperfusion. However, the regulation and function of vascular urocortin are unknown.


RESULTS
Immunohistochemistry showed definitive expression of urocortin in endothelial cells of coronary large arteries and microvessels from autopsied hearts. RT-PCR confirmed the expression of urocortin in human umbilical vein endothelial cells (HUVECs). Urocortin (10(-8) M) potently suppressed the generation of angiotensin II-induced reactive oxygen species (ROS) in HUVECs. Tumor necrosis factor-alpha and interferon-gamma increased the urocortin mRNA levels and its release from HUVECs. Incubation with pitavastatin (0.1-3.0 microM) significantly increased the urocortin mRNA levels and its release from HUVECs. Furthermore, treatment with pitavastatin (2 mg/day) for 4 weeks increased the serum urocortin level from 11.0 +/- 6.5 to 16.4 +/- 7.3 ng/ml in healthy volunteers.


CONCLUSIONS
Endothelial urocortin was upregulated by inflammatory cytokines and pitavastatin and suppressed ROS production in endothelial cells. Treatment with pitavastatin increased the serum urocortin level in human subjects. Thus, endothelial urocortin might protect cardiomyocytes in inflammatory lesions. Urocortin might partly explain the mechanisms of various pleiotropic effects of statins.
Honjo
Tomoyuki
T
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Inoue
Nobutaka
N
Shiraki
Rio
R
Kobayashi
Seiichi
S
Otsui
Kazunori
K
Takahashi
Motonori
M
Hirata
Ken-Ichi
K
Kawashima
Seinosuke
S
Yokozaki
Hiroshi
H
Yokoyama
Mitsuhiro
M
D000328:Adult; D000975:Antioxidants / Q000502:physiology*; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins; D015854:Up-Regulation; D054832:Urocortins
D000975:Antioxidants; D011804:Quinolines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D054832:Urocortins; D007371:Interferon-gamma; D003346:Corticotropin-Releasing Hormone; C108475:pitavastatin