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

Zhang, Yuzhu; Song, Haibo; Zhang, Yuan; Wu, Fei; Mei, Qian; Jiang, Miao; Wang, Fang; Zhang, Wen; Li, Liang; Shao, Lei; Li, Shiwu; Yang, Lijun; Zhang, Mingxiang; Wu, Qi; Tang, Dongqi

doi:10.1161/jaha.116.004031

Cited by 64 publications

(49 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lee et al (20) showed that circulating irisin levels were negatively associated with carotid intima-media thickness in peritoneal dialysis patients. In some rodent studies, the mechanisms underlying the protective effects of irisin on atherosclerosis are clarifying (11,12,21). However, our findings are in conflict with those of a number of studies showing that circulating irisin may negatively affect cardiovascular disease or risk factors.…”

Section: Discussioncontrasting

confidence: 79%

“…Irisin is secreted into the circulation after cleavage from the membrane protein FNDC5 and activates expression of mitochondrial uncoupling protein-1 (UCP-1) and "browning" of white adipose tissue (8), leading to increased insulin sensitivity, improved glucose tolerance, lower body weight, and decreased fat mass (9,10). Several studies have shown that irisin also promotes endothelial function and inhibits atherosclerosis (11,12). However, to the best of our knowledge, the association between myokines, especially irisin, and the characteristics of coronary plaques is still unclear.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Clinical Impact of Circulating Irisin on Classified Coronary Plaque Characteristics

Hirayama

Ishii

Kikuchi

et al. 2018

The Journal of Applied Laboratory Medicine

View full text Add to dashboard Cite

Background Myokines are hormones secreted by skeletal muscles during physical activity. Low myokine levels may contribute to metabolic dysfunction and cardiovascular disorders. Irisin, a newly identified myokine, has been the focus of recent research. The aim of the present study was to analyze the association between circulating irisin levels and tissue characteristics of nonculprit left main coronary artery (LMCA) plaques with the use of integrated backscatter (IB) intravascular ultrasound (IVUS). Methods This observational study enrolled 55 Japanese patients following successful percutaneous coronary intervention for lesions in the left anterior descending arteries or left circumflex arteries. Circulating myokine levels, including myostatin, brain-derived neurotrophic factor, and irisin, were measured by an enzyme-linked immunosorbent assay. Tissue characteristics of LMCA plaque were evaluated by IB-IVUS. Results Circulating irisin levels were negatively associated with percent lipid volume (%LV) [r = −0.31 (95% CI, −2.52 to −0.21), P = 0.02] and positively associated with percent fibrous volume (%FV) [r = 0.32 (95% CI, 0.22–2.20), P = 0.02]. The optimal cutoff value of circulating irisin for the prediction of lipid-rich LMCA plaques was 6.02 μg/mL [area under the curve = 0.713, P < 0.01 (95% CI, 0.58–0.85)]. Multivariate linear regression analysis identified circulating irisin levels as independent predictors for %LV and %FV of the LMCA [β = −0.29 (95% CI, −2.53 to −0.07), P = 0.04 and β = 0.30 (95% CI, 0.10–2.23), P = 0.03, respectively]. Conclusions Circulating irisin levels are significantly associated with tissue characteristics of nonculprit LMCA plaques.

show abstract

Section: Discussioncontrasting

confidence: 79%

mentioning

confidence: 99%

Clinical Impact of Circulating Irisin on Classified Coronary Plaque Characteristics

Hirayama

Ishii

Kikuchi

et al. 2018

The Journal of Applied Laboratory Medicine

View full text Add to dashboard Cite

show abstract

“…Several studies have also suggested that irisin treatment reduced the degree of carotid and aortic atherosclerotic plaque in apolipoprotein E-knock out mice, an atherosclerotic model [ 50 , 51 , 52 ]. These studies demonstrated that irisin may suppress neointima formation, endothelial injury, and inflammation in the atherosclerotic vasculature, implying a potential role of irisin in treating atherosclerosis [ 50 , 51 , 52 ]. The findings of the previous studies suggest that irisin may be a therapeutic target for vascular complications and dysfunction induced by metabolic abnormality.…”

Section: The Potential Role Of Irisin In Vascular Reactivity and Amentioning

confidence: 99%

The Potential Role of Irisin in Vascular Function and Atherosclerosis: A Review

Byun

Lee

2020

IJMS

View full text Add to dashboard Cite

Exercise is an effective intervention for both the prevention and the treatment of obesity and insulin resistance because skeletal muscle secretes many bioactive proteins that contribute to the beneficial effect of exercise. It has been revealed that irisin plays an important role in metabolic homeostasis and both acute and chronic exercises increase circulating irisin in experimental animal models and in humans. Although previous studies have reported that the irisin-related signaling mechanism may play a beneficial role in the treatment of metabolic diseases including obesity, metabolic syndrome, insulin resistance, and diabetes mellitus, studies on whether irisin plays a key role in vascular function and vascular complications are still insufficient. Therefore, the current review aims to summarize the accumulating evidence showing the potential role of irisin, especially in vascular reactivity and vascular abnormalities such as atherosclerosis.

show abstract

“…Liu et al found that Fndc5 deficiency aggravated whereas FNDC5 overexpression prevented obesity-related hyperlipemia, hepatic lipid accumulation, and impaired fatty acid oxidation and autophagy in the liver [20]. Except for the beneficial role in metabolic disorders, recent studies also implicated that FNDC5/Irisin was involved in regulating various cardiovascular diseases, such as atherosclerosis, hypertension, myocardial ischemia/reperfusion injury, and cardiac hypertrophy [21][22][23][24]. Besides, numerous researches verified that FNDC5 overexpression or irisin supplementation could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis [25,26].…”

Section: Introductionmentioning

confidence: 99%

FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT

et al. 2019

View full text Add to dashboard Cite

Oxidative stress and cardiomyocyte apoptosis play critical roles in doxorubicin (DOX)-induced cardiotoxicity. Previous studies indicated that fibronectin type III domain-containing 5 (FNDC5) and its cleaved form, irisin, could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis, however, its role in DOX-induced cardiotoxicity remains unknown. Our present study aimed to investigate the role and underlying mechanism of FNDC5 on oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity. Cardiomyocyte-specific FNDC5 overexpression was achieved using an adeno-associated virus system, and then the mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. Herein, we found that FNDC5 expression was downregulated in DOX-treated murine hearts and cardiomyocytes. Fndc5 deficiency resulted in increased oxidative damage and apoptosis in H9C2 cells under basal conditions, imitating the phenotype of DOX-induced cardiomyopathy in vitro, conversely, FNDC5 overexpression or irisin treatment alleviated DOX-induced oxidative stress and cardiomyocyte apoptosis in vivo and in vitro. Mechanistically, we identified that FNDC5/Irisin activated AKT/mTOR signaling and decreased DOX-induced cardiomyocyte apoptosis, and moreover, we provided direct evidence that the anti-oxidant effect of FNDC5/Irisin was mediated by the AKT/GSK3β/FYN/Nrf2 axis in an mTOR-independent manner. And we also demonstrated that heat shock protein 20 was responsible for the activation of AKT caused by FNDC5/Irisin. In line with the data in acute model, we also found that FNDC5/Irisin exerted beneficial effects in chronic model of DOX-induced cardiotoxicity (5 mg/kg, i.p., once a week for three times, the total cumulative dose is 15 mg/kg) in mice. Based on these findings, we supposed that FNDC5/Irisin was a potential therapeutic agent against DOX-induced cardiotoxicity.

show abstract

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

Cited by 64 publications

References 40 publications

Clinical Impact of Circulating Irisin on Classified Coronary Plaque Characteristics

Clinical Impact of Circulating Irisin on Classified Coronary Plaque Characteristics

The Potential Role of Irisin in Vascular Function and Atherosclerosis: A Review

FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT

Contact Info

Product

Resources

About