Role of miR-195 in Aortic Aneurysmal Disease

Zampetaki, Anna; Attia, Rizwan; Mayr, Ursula; Gomes, Renata S. M.; Phinikaridou, Alkystis; Yin, Xiaoke; Langley, Sarah R.; Willeit, Peter; Lu, Ruifang; Fanshawe, Bruce; Fava, Marika; Barallobre-Barreiro, Javier; Molenaar, Chris; So, Po‐Wah; Abbas, Abeera; Jahangiri, Marjan; Waltham, Matthew; Botnar, René M.; Smith, Alberto; Mayr, Manuel

doi:10.1161/circresaha.115.304361

Cited by 94 publications

(102 citation statements)

References 32 publications

(13 reference statements)

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“…OR, odds ratio. including targets that would not have been anticipated based on current bioinformatics prediction models (11,16). To complement our clinical studies, we used a proteomics approach to identify putative protein targets of miR-27b and miR-320a in the secretome of ECs.…”

Section: Proteomics For Mirna Target Identificationmentioning

confidence: 99%

Angiogenic microRNAs Linked to Incidence and Progression of Diabetic Retinopathy in Type 1 Diabetes

et al. 2015

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Circulating microRNAs (miRNAs) have emerged as novel biomarkers of diabetes. The current study focuses on the role of circulating miRNAs in patients with type 1 diabetes and their association with diabetic retinopathy. A total of 29 miRNAs were quantified in serum samples (n = 300) using a nested case-control study design in two prospective cohorts of the DIabetic REtinopathy Candesartan Trial (DIRECT): PROTECT-1 and PREVENT-1. The PREVENT-1 trial included patients without retinopathy at baseline; the PROTECT-1 trial included patients with nonproliferative retinopathy at baseline. Two miRNAs previously implicated in angiogenesis, miR-27b and miR-320a, were associated with incidence and with progression of retinopathy: the odds ratio per SD higher miR-27b was 0.57 (95% CI 0.40, 0.82; P = 0.002) in PREVENT-1, 0.78 (0.57, 1.07; P = 0.124) in PROTECT-1, and 0.67 (0.50, 0.92; P = 0.012) combined. The respective odds ratios for higher miR-320a were 1.57 (1.07, 2.31; P = 0.020), 1.43 (1.05, 1.94; P = 0.021), and 1.48 (1.17, 1.88; P = 0.001). Proteomics analyses in endothelial cells returned the antiangiogenic protein thrombospondin-1 as a common target of both miRNAs. Our study identifies two angiogenic miRNAs, miR-320a and miR-27b, as potential biomarkers for diabetic retinopathy.Recent studies have begun to unveil a powerful and unexpected role of microRNAs (miRNAs) in numerous forms of diseases, providing a unique opportunity to translate this knowledge into the clinical setting in the form of miRNA-based therapeutics and diagnostics (1,2). miRNAs are small noncoding RNAs with cell-type specific expression patterns that orchestrate biological networks by modulating gene expression. miRNAs form base pairs with their target messenger RNAs and mediate gene silencing, often regulating multiple proteins within the same biological pathways. Given their importance in angiogenesis, along with the technical feasibility in manipulating their function in vivo, vascular miRNAs have become central targets for therapeutic manipulation, including diabetes (3).Additionally, miRNAs circulate in blood. We have previously performed the first systematic analysis of circulating miRNAs in a population-based study (the Bruneck Study) and identified distinct miRNA signatures associated with type 2 diabetes (4) and risk of myocardial infarction (5). We have also highlighted their platelet origin (6) and applied concepts of network topology to explore their biomarker potential (7). Exciting opportunities exist to pursue miRNAs as novel biomarkers for risk estimation and patient stratification (8).The current study addresses the role of circulating miRNAs in patients with type 1 diabetes (T1D) and their association with microvascular complications, in particular, diabetic retinopathy. Our aims were threefold: first, to evaluate whether miRNA profiles are independently associated with retinopathy development and progression in diabetes; second, to quantify the incremental discriminatory power of miRNAs over and above traditional risk markers; ...

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Section: Proteomics For Mirna Target Identificationmentioning

confidence: 99%

Angiogenic microRNAs Linked to Incidence and Progression of Diabetic Retinopathy in Type 1 Diabetes

et al. 2015

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“…The available evidence supports the concept that a link exists between circulating IGF-1 levels and miRNA expression (Bake et al 2014;Bates et al 2010;Fenn et al 2013;Marino et al 2010;Victoria et al 2015). Demonstration of IGF-1-dependent changes in miRNA biology in the vasculature is particularly important (Bonauer et al 2009;Chen et al 2015;Doebele et al n.d.;Hergenreider et al 2012;Kim et al 2014;Kuehbacher et al 2007;Leung et al 2013;Lovren et al 2012;O'Rourke and Olson 2011;Rotllan et al 2013;Stellos and Dimmeler 2014;Weber et al 2014;Zampetaki et al 2014) as changes in miRNA expression have been causally linked to the development of cardiovascular aging phenotypes (Boon et al 2013;Csiszar et al 2014;Ungvari et al 2013) and the pathogenesis of cardiovascular diseases (Ono et al 2011).…”

Section: Discussionmentioning

confidence: 63%

“…There is growing evidence that miRNAs control lifespan and the pace of aging in model organisms (Boehm and Slack 2005;Grillari and GrillariVoglauer n.d.;Ibanez-Ventoso et al 2006) and that changes in miRNA expression profile also have a role in mammalian aging (Bates et al n.d.;Inukai et al 2012;Inukai and Slack 2013;Ito et al 2010;Maes et al 2008;Mercken et al 2013;Smith-Vikos and Slack 2012;Ungvari et al 2013;Zhang et al 2012;Zovoilis et al 2011). Importantly, miRNAs were also reported to regulate several important aspects of endothelial biology and vascular function (Bonauer et al 2009;Chen et al 2015;Doebele et al n.d.;Hergenreider et al 2012;Kim et al 2014;Kuehbacher et al 2007;Leung et al 2013;Lovren et al 2012;O'Rourke and Olson 2011;Rotllan et al 2013;Stellos and Dimmeler 2014;Weber et al 2014;Zampetaki et al 2014). Further, age-related changes in miRNA expression were shown to contribute to the development of cardiovascular aging phenotypes (Boon et al 2013;Csiszar et al 2014;Ungvari et al 2013) and the pathogenesis of cardiovascular diseases (Ono et al 2011).…”

Section: Introductionmentioning

confidence: 99%

IGF-1 deficiency in a critical period early in life influences the vascular aging phenotype in mice by altering miRNA-mediated post-transcriptional gene regulation: implications for the developmental origins of health and disease hypothesis

Tarantini

Giles

Wren

et al. 2016

AGE

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Epidemiological findings support the concept of Developmental Origins of Health and Disease, suggesting that early-life hormonal influences during a sensitive period of development have a fundamental impact on vascular health later in life. The endocrine changes that occur during development are highly conserved across mammalian species and include dramatic increases in circulating IGF-1 levels during adolescence. The present study was designed to characterize the effect of developmental IGF-1 deficiency on the vascular aging phenotype. To achieve that goal, early-onset endocrine IGF-1 deficiency was induced in mice by knockdown of IGF-1 in the liver using Cre-lox technology (Igf1 f/f mice crossed with mice expressing albumindriven Cre recombinase). This model exhibits lowcirculating IGF-1 levels during the peripubertal phase of development, which is critical for the biology of aging. Due to the emergence of miRNAs as important regulators of the vascular aging phenotype, the effect of early-life IGF-1 deficiency on miRNA expression profile in the aorta was examined in animals at 27 months of age. We found that developmental IGF-1 deficiency elicits persisting late-life changes in miRNA expression in the vasculature, which significantly differed from AGE (2016) 38:239-258

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“…Indeed, some recent studies clearly demonstrated the roles of miRNAs in the development of AAA [41][42][43][44]. Zampetaki et al [45] examined miR-195, a member of the miR-15 family. The authors performed proteomic analysis of the secretome of murine aortic smooth muscle cells, after miR-195 manipulation, confirming that miR-195 regulates numerous ECM elements such collagens (COL1A1, COL1A2, and COL3A1).…”

Section: Resultsmentioning

confidence: 99%