Irisin relaxes mouse mesenteric arteries through endothelium-dependent and endothelium-independent mechanisms

Jiang, Miao; Wan, Fangzhu; Wang, Fang; Wu, Qi

doi:10.1016/j.bbrc.2015.11.040

Cited by 42 publications

(32 citation statements)

References 18 publications

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“…Although irisin has been reported to dilate rat mesenteric arteries through ATP‐sensitive potassium channels, this effect was noted at micromolar concentrations of irisin, much higher than the nanomolar concentrations of circulating irisin, used in the current report . The ability of higher concentrations of irisin to relax mouse mesenteric arteries has also been reported to be independent of PGI 2 . In additional studies, we found that irisin concentration‐ and time‐dependently enhanced the phosphorylation of eNOS from endothelial cells and mesenteric arteries, an effect that was blocked by L‐NAME.…”

Section: Discussioncontrasting

confidence: 45%

“…NO produced in Ach‐induced vasodilation is from endothelial cells, and irisin‐evoked relaxation of mesenteric arteries from mice has been reported to be partially blocked by the NOS inhibitor, L‐NAME . Because the irisin sequence is highly conserved among species, we determined the effect of irisin on NO production in human coronary endothelial cells.…”

Section: Resultsmentioning

confidence: 99%

“…Zhang et al and Jiang et al have reported that irisin (0.1–100 μmol/L) caused endothelium‐dependent and ‐independent vasodilation of arteries preconstricted with phenylephrine in mice and rats . Zhang et al also reported that bolus injections (2 minutes) of high doses of irisin (0.625–4 μg) decreased the blood pressure of Sprague‐Dawley and spontaneously hypertensive rats (SHRs) .…”

mentioning

confidence: 99%

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Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK‐Akt‐eNOS‐NO Pathway in the Spontaneously Hypertensive Rat

Han

Wang

et al. 2016

JAHA

117

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BackgroundExercise is a major nonpharmacological treatment for hypertension, but its underlying mechanisms are still not completely elucidated. Irisin, a polypeptide containing 112 amino acids, which is secreted mainly by skeletal muscle cells during exercise, exerts a protective role in metabolic diseases, such as diabetes mellitus and obesity. Because of the close relationship between irisin and metabolic diseases, we hypothesized that irisin may play a role in the regulation of blood pressure.Methods and ResultsBlood pressures of male Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were monitored through the carotid artery. Our study found that acute intravenous injection of irisin reduced blood pressure in SHRs, but not WKY rats. Irisin, by itself, had no direct vasorelaxing effect in phenylephrine‐preconstricted mesenteric arteries from SHRs. However, irisin augmented the acetylcholine‐induced vasorelaxation in mesenteric arteries from SHRs that could be reversed by Nω‐nitro‐l‐arginine‐methyl ester (L‐NAME; 100 μmol/L), indicating a role of nitric oxide (NO) in this action. Indeed, irisin increased NO production and phosphorylation of endothelial nirtic oxide synthase (eNOS) in endothelial cells. 5′‐AMP‐activated protein kinase (AMPK) was involved in the vasorelaxing effect of irisin because compound C (20 μmol/L), an AMPK inhibitor, blocked the irisin‐mediated increase in phosphorylation of eNOS and protein kinase B (Akt) in endothelial cells and vasodilation in mesenteric arteries.ConclusionsWe conclude that acute administration of irisin lowers blood pressure of SHRs by amelioration of endothelial dysfunction of the mesenteric artery through the AMPK‐Akt‐eNOS‐NO signaling pathway.

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Section: Discussioncontrasting

confidence: 45%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK‐Akt‐eNOS‐NO Pathway in the Spontaneously Hypertensive Rat

Han

Wang

et al. 2016

JAHA

117

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“…It has been reported that serum irisin levels are significantly lower in patients with obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome . Intriguingly, a growing number of studies have shown that irisin improves endothelial function in patients with type 2 diabetes and obese patients . In addition, we have demonstrated that irisin can promote human umbilical vein endothelial cell (HUVEC) proliferation and angiogenesis via the ERK signaling pathway .…”

Section: Introductionmentioning

confidence: 75%

Irisin Inhibits Atherosclerosis by Promoting Endothelial Proliferation Through microRNA126‐5p

Zhang

Song

Zhang

et al. 2016

JAHA

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Background Irisin is a newly discovered myokine that has been considered a promising candidate for the treatment of cardiovascular disease through improving endothelial function. However, little is known about the role of irisin in the progression of atherosclerosis. Methods and Results We used a carotid partial ligation model of apolipoprotein E–deficient mice fed on a high‐cholesterol diet to test the anti‐atherosclerosis effect of irisin. Irisin treatment significantly suppressed carotid neointima formation. It was associated with increased endothelial cell proliferation. In addition, irisin promoted human umbilical vein endothelial cell survival via upregulating microRNA126‐5p expression through the ERK signaling pathway. Inhibition of microRNA126‐5p using the microRNA126‐5p inhibitor abolished the prosurvival effect. The same results were demonstrated in vivo as the expression of microRNA126‐5p noticeably increased in ligated carotid artery after irisin treatment. Furthermore, in vivo blockade of microRNA126‐5p expression using the antagomir abolished the inhibitory effects of irisin on neointima formation, lesional lipid deposition, macrophage area, and the pro‐proliferation effects on endothelial cells. Conclusions Taken together, our study demonstrates that irisin significantly reduces atherosclerosis in apolipoprotein E–deficient mice via promoting endothelial cell proliferation through microRNA126‐5p, which may have a direct therapeutic effect on atherosclerotic diseases.

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“…Collectively, the data show that irisin increases after exercise, is linked to browning of AT, increases energy expenditure (Bostrom et al ., ) and is associated with improvements of vascular function and insulin sensitivity in mice (Jiang et al ., ; Lu et al ., ). Nonetheless, clarification of the regulatory mechanisms of irisin levels and its physiological consequences in obese and lean human subjects are questions to future interventional studies.…”

Section: Local Control Of Exercise On At: Myokinesmentioning

confidence: 99%

Exercise effects on perivascular adipose tissue: endocrine and paracrine determinants of vascular function

Boa

Yudkin

Hinsbergh

et al. 2017

British J Pharmacology

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Obesity is a global epidemic, accompanied by increased risk of type 2 diabetes and cardiovascular disease. Adipose tissue hypertrophy is associated with adipose tissue inflammation, which alters the secretion of adipose tissue‐derived bioactive products, known as adipokines. Adipokines determine vessel wall properties such as smooth muscle tone and vessel wall inflammation. Exercise is a mainstay of prevention of chronic, non‐communicable diseases, type 2 diabetes and cardiovascular disease in particular. Aside from reducing adipose tissue mass, exercise has been shown to reduce inflammatory activity in this tissue. Mechanistically, contracting muscles release bioactive molecules known as myokines, which alter the metabolic phenotype of adipose tissue. In adipose tissue, myokines induce browning, enhance fatty acid oxidation and improve insulin sensitivity. In the past years, the perivascular adipose tissue (PVAT) which surrounds the vasculature, has been shown to control vascular tone and inflammation through local release of adipokines. In obesity, an increase in mass and inflammation of PVAT culminate in dysregulation of adipokine secretion, which contributes to vascular dysfunction. This review describes our current understanding of the mechanisms by which active muscles interact with adipose tissue and improve vascular function. Aside from the exercise‐dependent regulation of canonical adipose tissue function, we will focus on the interactions between skeletal muscle and PVAT and the role of novel myokines, such as IL‐15, FGF21 and irisin, in these interactions. Linked Articles This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc

show abstract

Irisin relaxes mouse mesenteric arteries through endothelium-dependent and endothelium-independent mechanisms

Cited by 42 publications

References 18 publications

Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK‐Akt‐eNOS‐NO Pathway in the Spontaneously Hypertensive Rat

Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK‐Akt‐eNOS‐NO Pathway in the Spontaneously Hypertensive Rat

Irisin Inhibits Atherosclerosis by Promoting Endothelial Proliferation Through microRNA126‐5p

Exercise effects on perivascular adipose tissue: endocrine and paracrine determinants of vascular function

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