424-P: HDL miR-181c as a Novel Biomarker for Diabetic Vascular Complications in Australian Aboriginal People

Abstract

Diabetes is a major burden on Australia’s Indigenous population, with high rates of disease and vascular complications. Diabetic vascular complications are associated with impaired ischemia-driven angiogenesis. MicroRNAs (miRNAs) are known to regulate angiogenesis. We have recently identified a novel anti-angiogenic role for miR-181c. High-density lipoproteins (HDL) are associated with reduced rates of diabetic complications and serve as carriers of miRNAs in the circulation. HDL miRNA profiles differ in disease states. We sought to determine if circulating miR-181c levels reflect the severity of diabetic complications in Australian Aboriginal people. HDL was isolated from plasma samples of Australian Aboriginal participants with or without diabetes and associated complications living in regional South Australia; and a cohort of non-Indigenous participants without diabetes. We found that HDL miR-181c levels were strikingly elevated in the group of Aboriginal people with diabetic complications. However, plasma miR-181c levels were overall lower in Australian Aboriginal participants compared to the non-Indigenous group. Angiogenic capacity of isolated HDL was assessed in vitro using the Matrigel tubulogenesis assay. Under high glucose (25 mM) conditions, cells treated with HDL from the group of Aboriginal people with diabetic complications had a reduced capacity to form tubules and had lower mRNA levels of the hypoxia angiogenic transcription factor HIF-1α compared to all other groups. This attenuation of pro-angiogenic capacity may be attributed to the concurrent increase in cellular miR-181c levels. In conclusion, HDL from Aboriginal people with diabetic complications had reduced angiogenic capacity, highlighting its impaired function in the diabetic state and is potentially linked to the increased levels of the anti-angiogenic miRNA miR-181c. HDL miR-181c may be a novel biomarker for the extent of diabetic complications in Australian Aboriginal people. Disclosure K.R. Morrison: None. C. Bursill: None. E. Solly: None. T. Shemesh: None. S. Nicholls: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Cerenis, CSL Behring, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Omthera, Pfizer Inc., Resverlogix Corp., Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; Amgen Inc., AstraZeneca, Athernova, Cerenis, Eli Lilly and Company, InfraReDx, Novartis Pharmaceuticals Corporation, Resverlogix Corp., Sanofi. A.D. Brown: None. J.T.M. Tan: None.