Endothelial Urocortin Has Potent Antioxidative Properties and Is Upregulated by Inflammatory Cytokines and Pitavastatin

Honjo, Tomoyuki; Inoue, N.; Shiraki, Rio; Kobayashi, Seiichi; Otsui, Kazunori; Takahashi, Motonori; Hirata, Ken‐ichi; Kawashima, Seinosuke; Yokozaki, Hiroshi; Yokoyama, Mitsuhiro

doi:10.1159/000090132

Cited by 46 publications

(44 citation statements)

References 59 publications

(43 reference statements)

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“…For instance, it was shown that proinflammatory cytokines, such as TNFα and IFNγ, upregulated UCN1 protein expression in human umbilical vein endothelial cells, while UCN1 effectively attenuated the generation of ROS induced by Ang II [103]. In another study, it was found that UCN1 suppressed the LPSinduced upregulation of MCP1 and ICAM1 in human endothelial cells [100].…”

Section: Urocortinmentioning

confidence: 99%

Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

Fraga‐Silva

Trachet²,

Stergiopulos³

2015

CPD

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Abdominal aortic aneurysm (AAA) is a local expansion of the abdominal aorta wall caused by a complex multifactorial maladaptive vascular remodeling. Despite recent advances in the management of cardiovascular diseases, there currently is no established drug therapy for AAA. Since the probability of death from a ruptured AAA still remains high, preventive elective repair of AAAs larger than 5.5 cm in luminal diameter is considered the best treatment option. However, perioperative complications are problematic as elective AAA repair comes with numerous intrinsic risks. Impelled by the need of improving AAA therapy, significant efforts have been made to identify pharmacological tools that would slow down AAA enlargement and lower the risk of rupture, thereby reducing the necessity of surgical intervention. In this review, we discuss recent findings addressing molecular targets that could potentially treat AAA, particularly addressing: statins, classical renin angiotensin system (RAS) blockers, the protective arm of RAS, renin inhibitors, tetracyclines, interleukin-1β inhibition, anti-angiogenic agents and urocortins.

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Section: Urocortinmentioning

confidence: 99%

Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

Fraga‐Silva

Trachet²,

Stergiopulos³

2015

CPD

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“…In addition, one study showed that pitavastatindirectlyinhibitstheformationofROSin endothelialcells 118) .Therefore,individualstatinsexert distinct antioxidant effects via diverse mechanisms and/ortheiractionsinvariouscellsystems.…”

Section: Role Of the Antioxidant And Anti-inflammatory Effects Of Stamentioning

confidence: 99%

Antioxidant Effects of Statins in the Management of Cardiometabolic Disorders

Lim

Barter

2014

JAT

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Redox systems are key players in vascular health. A shift in redox homeostasis-that results in an imbalance between reactive oxygen species (ROS) generation and endogenous antioxidant defenses has the potential to create a state of oxidative stress that subsequently plays a role in the pathogenesis of a number of diseases, including those of the cardiovascular and metabolic system. Statins, which are primarily used to reduce the concentration of low-density lipoprotein cholesterol, have also been shown to reduce oxidative stress by modulating redox systems.Studies conducted both in vitro and in vivo support the role of oxidative stress in the development of atherosclerosis and cardiovascular diseases. Oxidative stress may also be responsible for various diabetic complications and the development of fatty liver. Statins reduce oxidative stress by blocking the generation of ROS and reducing the NAD＋/NADH ratio. These drugs also have effects on nitric oxide synthase, lipid peroxidation and the adiponectin levels.It is possible that the antioxidant properties of statins contribute to their protective cardiovascular effects, independent of the lipid-lowering actions of these agents. However, possible adverse effects of statins on glucose homeostasis may be related to the redox system. Therefore, studies investigating the modulation of redox signaling by statins are warranted. J Atheroscler Thromb, 2014; 21:997-1010.

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“…These findings suggest that Ucn I and its related peptides may be regulated by inflammatory cytokines, such as LPS and TNF-a, and may play a pathophysiological role in the diseased heart because CRH-R2 signaling in the heart may be very important for adaptation to cardiac stress in pathological conditions (Coste et al 2000). Ucn I may be regulated in response to oxidative stress, thereby exerting a vasoprotective role against the oxidative stress caused by angiotensin II (Ang II) in HUVECs (Honjo et al 2006). We hypothesized that Ucn I and its related peptides may be regulated by inflammatory and/or oxidative stress(es) in the diseased heart.…”

Section: Introductionmentioning

confidence: 99%

“…Urocortin (murine urocortin: Ucn, human urocortin: UCN) I, Ucn II, and Ucn III, the members of corticotropin-releasing hormone (CRH)-related peptides, have various actions on the cardiovascular system via cAMP-dependent pathways and the extracellularly regulated kinase 1/2 pathway (Ikeda et al 1998, 2002, 2005a, Brar et al 2004a, Honjo et al 2006. We previously reported the pathophysiological involvement of UCN I in cardiomyopathies (Ikeda et al 2003), in which a patient's plasma concentration of tumor necrosis factor (TNF)-a increased (Matsumori et al 1994).…”

Section: Introductionmentioning

confidence: 99%

“…TNF-a can produce various deleterious effects when expressed in large amounts and it is produced in the heart by both cardiomyocytes and resident macrophages under conditions of cardiac stress (Sarzi-Puttini et al 2005). In addition, Ucn I was up-regulated by TNF-a in human umbilical vein endothelial cells (Honjo et al 2006), and, in turn, CRH type 2 receptor (CRH-R2) was down-regulated by lipopolysaccarides (LPS) and TNF-a in the mouse heart (Ikeda et al 1998, Coste et al 2001. Because CRH-R2 was also downregulated by Ucn I in mouse cardiomyocytes (Heldwein et al 1997, Coste et al 2001 and in the mouse heart (Asaba et al 2000), we hypothesize that LPS and TNF-a may stimulate the release of endogenous ligand(s) for CRH-R2, such as CRH, Ucn I, Ucn II, and/or Ucn III, from the heart.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of urocortin I and its related peptide urocortin II by inflammatory and oxidative stresses in HL-1 cardiomyocytes

Ikeda¹,

Tojo²,

Inada³

et al. 2009

Journal of Molecular Endocrinology

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Despite our knowledge on the regulation of urocortin (Ucn) I and its related peptides in the heart, the possible involvement of cardiovascular stress substances, such as cytokines or angiotensin II (Ang II), on this regulation remains to be fully elucidated. We therefore evaluated the potential role of cardiovascular stress substances on the regulation of the Ucn-corticotropin-releasing hormone (CRH) receptor system in HL-1 cardiomyocytes using a Ucn I-specific RIA, conventional reverse transcription-PCR (RT-PCR) and quantitative real-time RT-PCR. Ucn I mRNA levels were shown to be up-regulated by lipopolysaccarides (LPS), tumor necrosis factor-a (TNF-a), Ang II, H 2 O 2 , and pyrrolidinedithiocarbamate (PDTC). The LPS-and Ang II-induced increase in Ucn I mRNA levels was abolished by tempol. In addition, the secretion of Ucn I from HL-1 cardiomyocytes was stimulated by LPS and TNF-a. On the contrary, Ucn II mRNA was increased by TNF-a alone and Ang II with tempol, and the TNF-a-induced increase in Ucn II mRNA was abolished by erythromycin and PDTC. These results suggested that Ucn I mRNA may be up-regulated by oxidative stress, whereas Ucn II mRNA may be up-regulated by the activated nuclear factor-kB, i.e. inflammatory stress. CRH-R2 mRNA may be negatively regulated by the increase in expression of Ucn I and/or Ucn II mRNA. In conclusion, the Ucn-CRH receptor system may be regulated by two major forms of cardiac stresses, i.e. oxidative and inflammatory stress, and may play a critical role in cardiac stress adaptation in heart diseases.

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Endothelial Urocortin Has Potent Antioxidative Properties and Is Upregulated by Inflammatory Cytokines and Pitavastatin

Cited by 46 publications

References 59 publications

Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

Antioxidant Effects of Statins in the Management of Cardiometabolic Disorders

Regulation of urocortin I and its related peptide urocortin II by inflammatory and oxidative stresses in HL-1 cardiomyocytes

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