MicroRNA-126 in Cardiovascular Disease - from Phenotype to Molecular Function

• Applicant: Dr. Christian Schulte
• Subject Area: Cardiology, Angiology ; Cell Biology
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 328550563

Cardiovascular disease (CVD) is the number one worldwide cause of mortality with increasing socioeconomic and health impact. Therefore, innovative strategies in the diagnosis and treatment of CVD are urgently needed to interfere with this progression. Endothelial dysfunction, atherosclerosis and angiogenesis play a crucial role in the development and maintenance of CVD. Molecular signalling pathways have a key function in vascular pathophysiology and are strongly influenced by microRNAs (miRNAs, miRs). MiRNAs are small non-coding RNAs that regulate gene expression and messenger RNA (mRNA) degradation. One of these miRNAs is miR-126-3p. It is highly enriched in endothelial cells (EC) and plays a central role in signalling pathways of angiogenesis and EC function. It is therefore an interesting molecule linked to atherosclerosis and CVD with diagnostic and therapeutic potential. Different target molecules that function as mediators of endothelial and vascular function have been identified to be regulated by miR-126-3p. Nevertheless, there is conflicting data with respect to miR-126-3p dysregulation and its contribution to atherosclerotic and CVD phenotypes. The present application seeks to address the question as to how the regulatory pathways of miR-126-3p associate with CVD in patients. Two independent epidemiological studies have identified miR-126-3p as prognostic circulating biomarker in CVD, and coronary artery disease in particular, underlining its significance in CVD. One of these studies was performed by the applicant and the other one by the hosting institution the proposed project is planned to be performed at. The aim of the proposed study is to investigate miR-126-3p-associated molecular pathways of vascular function and its dysregulation in CVD in a translational approach to interlink previous epidemiological findings and their causal cellular and molecular pathways. Comprehensive proteomics analysis of samples derived from in vitro cell culture and in vivo mouse models will be the analytical means to achieve the goal. The hosting institute is internationally renowned for its -omics research and provides all necessary equipment, which is important for performing the planned analyses. After return to Germany the applicant plans to use his gained knowledge on the one hand and the infrastructural possibilities as well as access to epidemiological patient data at the University Heart Centre Hamburg Eppendorf on the other to establish an own working group interlinking clinical findings in CVD with its molecular background. Additionally, the research study will strengthen and intensify the co-operation in molecular cardiovascular research between the hosting institution, Kings College in London, and the University Heart Centre Hamburg Eppendorf in order to build up an international scientific research network with optimal utilization of synergistic effects.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Manuel Mayr, Ph.D.