Vasoprotective Effects of Urocortin 1 against Atherosclerosis In Vitro and In Vivo

Hasegawa, Akinori; Sato, Kengo; Shirai, Ryuichi; Watanabe, Ryoji; Yamamoto, Keigo; Watanabe, K.; Nohtomi, Kyoko; Hirano, Tsutomu; Watanabe, Takuya

doi:10.1371/journal.pone.0110866

Cited by 23 publications

(85 citation statements)

References 45 publications

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“…Cells were fixed with 4% paraformaldehyde. Terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate‐biotin nick end labeling (TUNEL) staining was then performed using an In Situ Apoptosis Detection Kit (Takara Bio, Shiga, Japan) as described previously …”

Section: Methodsmentioning

confidence: 99%

“…Other than the accumulation of macrophage foam cells, migration and proliferation of vascular smooth muscle cells (VSMCs), EC proliferation, and production of extracellular matrix (ECM) components, such as the collagens, matrix metalloproteinases (MMPs), fibronectin, and elastin, all contribute to progression of atherosclerotic plaques. 21,22 In the present study, we assessed the modulatory effects of KP-10, in vitro, on the inflammatory response, proliferation, and adhesion (to monocytes) for HUVECs, foam cell formation in human monocyte-derived macrophages (HMDMs), and the migration, proliferation, and ECM production in human aortic smooth muscle cells (HASMCs). In vivo studies focused on the atherogenic effect of KP-10 and atheroprotective effect of a GPR54 antagonist in apolipoprotein E-deficient (ApoE À/À ) mice.…”

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confidence: 99%

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Potent Vasoconstrictor Kisspeptin‐10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist

Sato

Shirai

Hontani

et al. 2017

JAHA

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BackgroundKisspeptin‐10 (KP‐10), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor, GPR54, have currently received much attention in relation to pre‐eclampsia. However, it still remains unknown whether KP‐10 could affect atherogenesis.Methods and ResultsWe evaluated the effects of KP‐10 on human umbilical vein endothelial cells, human monocyte‐derived macrophages, human aortic smooth muscle cells in vitro, and atherosclerotic lesions in apolipoprotein E–deficient (ApoE−/−) mice in vivo. KP‐10 significantly increased the adhesion of human monocytes to human umbilical vein endothelial cells, which was significantly inhibited by pretreatment with P234, a GPR54 antagonist. KP‐10 stimulated mRNA expression of tumor necrosis factor‐α, interleukin‐6, monocyte chemotactic protein‐1, intercellular adhesion molecule‐1, vascular adhesion molecule‐1, and E‐selectin in human umbilical vein endothelial cells. KP‐10 significantly enhanced oxidized low‐density lipoprotein–induced foam cell formation associated with upregulation of CD36 and acyl‐CoA:cholesterol acyltransferase‐1 in human monocyte‐derived macrophages. In human aortic smooth muscle cells, KP‐10 significantly suppressed angiotensin II–induced migration and proliferation, but enhanced apoptosis and activities of matrix metalloproteinase (MMP)‐2 and MMP‐9 by upregulation of extracellular signal‐regulated kinase 1 and 2, p38, Bcl‐2‐associated X protein, and caspase‐3. Four‐week‐infusion of KP‐10 into ApoE−/− mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration and vascular inflammation as well as decreased intraplaque vascular smooth muscle cells contents. Proatherosclerotic effects of endogenous and exogenous KP‐10 were completely canceled by P234 infusion in ApoE−/− mice.ConclusionsOur results suggest that KP‐10 may contribute to accelerate the progression and instability of atheromatous plaques, leading to plaque rupture. The GPR54 antagonist may be useful for prevention and treatment of atherosclerosis. Thus, the KP‐10/GPR54 system may serve as a novel therapeutic target for atherosclerotic diseases.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Potent Vasoconstrictor Kisspeptin‐10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist

Sato

Shirai

Hontani

et al. 2017

JAHA

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“…In another study, it was found that UCN1 suppressed the LPSinduced upregulation of MCP1 and ICAM1 in human endothelial cells [100]. Moreover, in human aortic smooth muscle cells, UCN1 suppressed Ang II-induced migration, inhibit cell proliferation without inducing apoptosis and enhance the activities of MMP2 and MMP9 [100]. Others reported that UCN1 treatment inhibited cell proliferation and VEGF release in rat smooth muscle cells [104].…”

Section: Urocortinmentioning

confidence: 98%

“…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]. Moreover, in human aortic smooth muscle cells, UCN1 suppressed Ang II-induced migration, inhibit cell proliferation without inducing apoptosis and enhance the activities of MMP2 and MMP9 [100].…”

Section: Urocortinmentioning

confidence: 99%

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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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Natural and synthetic peptides in the cardiovascular diseases: An update on diagnostic and therapeutic potentials

Grieco¹,

Gómez-Monterrey²

2019

Archives of Biochemistry and Biophysics

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Vasoprotective Effects of Urocortin 1 against Atherosclerosis In Vitro and In Vivo

Cited by 23 publications

References 45 publications

Potent Vasoconstrictor Kisspeptin‐10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist

Potent Vasoconstrictor Kisspeptin‐10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist

Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

Natural and synthetic peptides in the cardiovascular diseases: An update on diagnostic and therapeutic potentials

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