MicroRNA 29b-dependent mechanisms of arterial stiffness in diabetes.

• Applicant: Dr. Isabel Nahal Schellinger
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2019 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 430929322

Patients with type 2 diabetes (T2D) suffer from an increased risk of developing cardiovascular diseases (CVD), e.g., hypertension, heart failure, myocardial infarction, and stroke. A critical link between T2D and the accompanying increased risk for CVD might be arterial stiffening, a major complication of T2D. Till now, many biological processes (including extracellular matrix (ECM) remodeling, calcification, inflammation, and oxidative stress) have been recognized to contribute to diabetes-related arterial stiffness. Still, specific strategies for intervention remain elusive.Lately, non-coding RNAs have been identified as key regulators of cellular function in health and disease. One subclass of these non-coding RNAs are microRNAs (miRs) that may modulate complex biological processes – such as arterial stiffening – by inhibiting multiple target genes and therefore serve as promising target for therapeutical intervention. Another subclass of interest are circular RNAs (circRNAs) that serve as miR sponges and valuable biomarkers due to their resistance to peripheral degradation.Preliminary data show that miR-29b is downregulated in human as well as murine aortic tissue, and potentially interferes with genes orchestrating vascular matrix remodeling. Furthermore, we hypothesize that circHIPK3 might act as miR-29b sponge in the context of T2D. Thus, the proposed project investigates mechanisms regulating miR-29b under diabetic conditions, in addition to the role of miR-29b itself as a potential regulator of diabetes-related arterial stiffness.

• DFG Programme: Research Grants