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

Anna Zampetaki; Peter Willeit; Simon Jonathan Burr; Xiaoke Yin; Sarah Raye Langley; Stefan Kiechl; Ronald Klein; Peter Rossing; Nishi Chaturvedi; Manuel Mayr

doi:10.2337/db15-0389

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

Anna Zampetaki, Peter Willeit, Simon Jonathan Burr, Xiaoke Yin, Sarah Raye Langley, Stefan Kiechl, Ronald Klein, Peter Rossing, Nishi Chaturvedi, Manuel Mayr

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Abstract

Circulating microRNAs (miRNAs) have emerged as novel biomarkers of diabetes. The present 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 programme): PROTECT-1 and PREVENT-1. The PREVENT-1 trial included patients without retinopathy at baseline; the PROTECT-1 trial included patients with non-proliferative 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 standard deviation 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 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 anti-angiogenic 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.

Original language	English
Pages (from-to)	216-227
Number of pages	11
Journal	Diabetes
Volume	65
Issue number	1
Early online date	22 Sept 2015
DOIs	https://doi.org/10.2337/db15-0389
Publication status	Published - 1 Jan 2016

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title = "Angiogenic MicroRNAs Linked to Incidence and Progression of Diabetic Retinopathy in Type 1 Diabetes",

abstract = "Circulating microRNAs (miRNAs) have emerged as novel biomarkers of diabetes. The present 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 programme): PROTECT-1 and PREVENT-1. The PREVENT-1 trial included patients without retinopathy at baseline; the PROTECT-1 trial included patients with non-proliferative 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 standard deviation 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 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 anti-angiogenic 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. ",

author = "Anna Zampetaki and Peter Willeit and Burr, {Simon Jonathan} and Xiaoke Yin and Langley, {Sarah Raye} and Stefan Kiechl and Ronald Klein and Peter Rossing and Nishi Chaturvedi and Manuel Mayr",

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AU - Zampetaki, Anna

AU - Willeit, Peter

AU - Burr, Simon Jonathan

AU - Yin, Xiaoke

AU - Langley, Sarah Raye

AU - Kiechl, Stefan

AU - Klein, Ronald

AU - Rossing, Peter

AU - Chaturvedi, Nishi

AU - Mayr, Manuel

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N2 - Circulating microRNAs (miRNAs) have emerged as novel biomarkers of diabetes. The present 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 programme): PROTECT-1 and PREVENT-1. The PREVENT-1 trial included patients without retinopathy at baseline; the PROTECT-1 trial included patients with non-proliferative 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 standard deviation 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 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 anti-angiogenic 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.

AB - Circulating microRNAs (miRNAs) have emerged as novel biomarkers of diabetes. The present 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 programme): PROTECT-1 and PREVENT-1. The PREVENT-1 trial included patients without retinopathy at baseline; the PROTECT-1 trial included patients with non-proliferative 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 standard deviation 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 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 anti-angiogenic 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.

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SP - 216

EP - 227

JO - Diabetes

JF - Diabetes

IS - 1

ER -

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

Abstract

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