Plasma MicroRNA-100 Is Associated With Coronary Plaque Vulnerability

Soeki, Takeshi; Yamaguchi, Koji; Niki, Toshiyuki; Uematsu, Etsuko; Bando, Shigenobu; Matsuura, Tomomi; Ise, Takayuki; Kusunose, Kenya; Hotchi, Junko; Tobiume, Takeshi; Yagi, Shusuke; Fukuda, Daiju; Taketani, Yuji; Igarashi, Takashi; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Sata, Masataka

doi:10.1253/circj.cj-14-0958

Cited by 32 publications

(24 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One explanation could be that Raitoharju et al 47 did not distinguish between stable and unstable plaque lesions as we did in our experimental setting. Our data suggest miR-100 as a potential biomarker of plaque vulnerability, and this is supported by a study of Soeki et al, 48 which provides evidence that miR-100 is released into the coronary circulation from lipid-rich plaques as a compensatory mechanism to stabilize the plaque by direct suppression of mTOR. In contrast to this study, Cipollone et al 49 described an increased expression of miR-100 in symptomatic human carotid artery lesions (defined by the presence of stroke) compared with asymptomatic ones.…”

Section: Discussionsupporting

confidence: 86%

MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy

Pankratz

Hohnloser

Bemtgen

et al. 2018

Circulation Research

101

View full text Add to dashboard Cite

Many attempts to modulate leukocyte-endothelial interaction to prevent or reduce excessive inflammatory reactions were made in the past. However, the basic regulatory principles of the endothelial inflammatory process remain unclear. It seems that the inhibition of individual components of the inflammatory cascade, for example, by a single antibody against an adhesion molecule, may not be enough to achieve a sustained effect on vascular inflammation.In the past years, microRNAs have been identified as important regulators of gene expression in a wide range of Molecular Medicine© 2017 American Heart Association, Inc. Rationale:The interaction of circulating cells within the vascular wall is a critical event in chronic inflammatory processes, such as atherosclerosis, but the control of the vascular inflammatory state is still largely unclear.Objective: This study was undertaken to characterize the function of the endothelial-enriched microRNA miR-100 during vascular inflammation and atherogenesis. Methods and Results:Based on a transcriptome analysis of endothelial cells after miR-100 overexpression, we identified miR-100 as a potent suppressor of endothelial adhesion molecule expression, resulting in attenuated leukocyte-endothelial interaction in vitro and in vivo as shown by flow cytometry and intravital imaging. Mechanistically, miR-100 directly repressed several components of mammalian target of rapamycin complex 1-signaling, including mammalian target of rapamycin and raptor, which resulted in a stimulation of endothelial autophagy and attenuated nuclear factor κB signaling in vitro and in vivo. In a low-density lipoprotein receptordeficient atherosclerotic mouse model, pharmacological inhibition of miR-100 resulted in enhanced plaque lesion formation and a higher macrophage content of the plaque, whereas a systemic miR-100 replacement therapy had protective effects and attenuated atherogenesis, resulting in a decrease of plaque area by 45%. Finally, analysis of miR-100 expression in >70 samples obtained during carotid endarterectomy revealed that local miR-100 expression was inversely correlated with inflammatory cell content in patients. Conclusions: In summary, we describe an anti-inflammatory function of miR-100 in the vascular response to injury and inflammation and identify an important novel modulator of mammalian target of rapamycin signaling and autophagy

show abstract

Section: Discussionsupporting

confidence: 86%

MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy

Pankratz

Hohnloser

Bemtgen

et al. 2018

Circulation Research

101

View full text Add to dashboard Cite

show abstract

“…42) Furthermore, we recently have found that plasma miR-100 levels are higher in the coronary sinus than in the aorta in patients with angina pectoris. 43) We also have found that transcoronary concentration gradients of circulating miR-100 are significantly correlated with the percentage of lipid volume and fibrous volume determined by integrated backscatter intravascular ultrasound. 43) These findings suggest that miR-100 might be released into the coronary circulation from vulnerable coronary plaques ( Figure 1) and might stabilize plaques at least in part by suppression of the mammalian target of rapamycin (mTOR) signaling pathway.…”

Section: )mentioning

confidence: 59%

“…43) We also have found that transcoronary concentration gradients of circulating miR-100 are significantly correlated with the percentage of lipid volume and fibrous volume determined by integrated backscatter intravascular ultrasound. 43) These findings suggest that miR-100 might be released into the coronary circulation from vulnerable coronary plaques ( Figure 1) and might stabilize plaques at least in part by suppression of the mammalian target of rapamycin (mTOR) signaling pathway. Altogether, the accumulated body of evidence indicates the potential usefulness of miRNAs as a novel type of atherosclerotic biomarker, promising rapid progress in the coming years.…”

Section: )mentioning

confidence: 59%

Inflammatory Biomarkers and Atherosclerosis

2016

Self Cite

View full text Add to dashboard Cite

SummaryAtherosclerosis has been regarded as a form of chronic vascular inflammation. Numerous biomarkers associated with inflammation have been identified as novel targets to monitor atherosclerosis and cardiovascular risk. C-reactive protein (CRP) is one of the most actively studied and established inflammatory biomarkers for cardiovascular events. However, CRP response is triggered by many disorders unrelated to cardiovascular disease, which interferes with the clinical application. This review describes established and traditional inflammatory biomarkers including CRP as well as novel inflammatory biomarkers reflective of local atherosclerotic inflammation. In addition, we focus on the potential usefulness of inflammatory biomarkers in developing anti-atherosclerotic therapeutic approaches. (Int Heart J 2016; 57: 134-139)

show abstract

“…In this study, miR-100, miR-297, and miR-758 were chosen as candidate genes after miRNA database prediction indicated that they interact with Col3a1, Agtr1a, and Col1a2, respectively. Previous studies have shown that plasma miR-100 is positively associated with coronary plaque vulnerability [72] can inhibit angiogenesis [73] and is involved in the development and growth of pancreatic cancer [74], while miR-297 is involved in septic shock [75]. In this study, the luciferase assay was used to demonstrate that miR-297 targets AGTR1 and promotes the proliferation of cardiomyocytes by regulating the expression of AGTR1 and CTGF.…”

Section: Discussionmentioning

confidence: 90%

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Wang

Zhang

Fang

et al. 2018

Biology of Reproduction

View full text Add to dashboard Cite

Epidemiological studies have revealed that offspring conceived by in vitro fertilization (IVF) have an elevated risk of cardiovascular malformations at birth, and are more predisposed to cardiovascular diseases. The renin-angiotensin system (RAS) plays an essential role in both the pathogenesis of congenital heart disease in fetuses and cardiovascular dysfunction in adults. This study aimed to assess the relative expression levels of genes in the RAS pathway in mice conceived using IVF, compared to natural mating with superovulation. Results demonstrated that expression of the angiotensin II receptor type 1 (AGTR1), connective tissue growth factor (CTGF), and collagen 3 (COL3), in the myocardial tissue of IVF-conceived mice, was elevated at 3 weeks, 10 weeks, and 1.5 years of age, when compared to their non-IVF counterparts. These data were supported by microRNA microarray analysis of the myocardial tissue of aged IVF-conceived mice, where miR-100, miR-297, and miR-758, which interact with COL3, AGTR1, and COL1 respectively, were upregulated when compared to naturally mated mice of the same age. Interestingly, bisulfite sequencing data indicated that IVF-conceived mice exhibited decreased methylation of CpG sites in Col1. In support of our in vivo investigations, miR-297 overexpression was shown to upregulate AGTR1 and CTGF, Effects of in vitro fertilization on myocardium, 2018, Vol. 99, No. 6 1277 and increased cell proliferation in cultured H9c2 cardiomyocytes. These findings indicate that the altered expression of RAS in myocardial tissue might contribute to cardiovascular malformation and/or dysfunction in IVF-conceived offspring. Furthermore, these cardiovascular abnormalities might be the result of altered DNA methylation and abnormal regulation of microRNAs. Summary SentenceAltered expression of the renin-angiotensin system in myocardial tissue might contribute to an increased risk of cardiovascular malformations and dysfunction in IVF offspring, and is involved in abnormal regulations of DNA methylation and microRNAs.

show abstract

Plasma MicroRNA-100 Is Associated With Coronary Plaque Vulnerability

Cited by 32 publications

References 32 publications

MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy

MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy

Inflammatory Biomarkers and Atherosclerosis

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Contact Info

Product

Resources

About