Neuroimmune guidance cues, MicroRNAs & Inflammatory responses: Sex differences in CardioVascular Diseases

Consortium name: MISs-CVD

MISs-CVD is a research consortium funded by   ERA-CVD (European Research Area Network on Cardiovascular Diseases) Joint Transnational Call 2020. Project partners are Janine van Gils from University of Leiden, Netherlands and Katey Rayner from University of  Ottawa, Canada and Hilal Kazan from Antalya Bilim University. 

Despite advances in the diagnosis, prevention and treatment of cardiovascular disease, the risk of coronary artery disease in women increases dramatically after menopause, and cardiovascular disease remains the number one cause of premature death in women. There is an urgent need to better understand the precise differences in atherosclerosis development in males and females. In this MISs-CVD proposal, we will leverage our combined expertise in immune cell trafficking (van Gils, Rayner), NGCs (van Gils), miRNA regulation (Rayner, Kazan) and computational modelling (Kazan) using state-of-the-art approaches to better understand sex-specific biology in the vessel wall. This ambitious interdisciplinary project combines expertise in molecular cell biology, bioinformatics and physiology and aims to 1) deliver a detailed characterization of sex-biased miRNAs targeting NGCs found in monocytes, ECs and macrophages and their alterations under atherogenic conditions, and 2) corroborate the functional implications of these sex-biased miRNAs targeting NGCs in human (patho)physiology. Together, this will enhance our understanding in leukocyte recruitment and accumulation in atherosclerosis development, and is likely to accelerate the diagnosis, treatment and prevention of atherosclerosis to improve evidence-based treatment of cardiovascular disease in not only women, but also in men, to reduce the global burden of this disease.

Our latest results can be founded in the following presentation.

Project members at Antalya Bilim University:
Aissa Houdjedj, PhD student at Akdeniz University
Yacine Marouf, MSc student at Antalya Bilim University. 
Onur Doğan, undergraduate student at  Antalya Bilim University.

M. Krichen, undergraduate student at Antalya Bilim University.

Our latest results can be founded in the following presentation

Resulting publications:
•D Karunakaran,...., JM van Gils, KJ Rayner (2021)  RIPK1 Expression Associates With Inflammation in Early Atherosclerosis in Humans and Can Be Therapeutically Silenced to Reduce NF-κB Activation and Atherogenesis in Mice. Circulation; 143(2):163-177.    

•MA Nguyen,…H Kazan, .., KJ Rayner (2022) miR-223 Exerts Translational Control of Cholesterol Efflux and Inflammatory Pathways in Atherosclerosis. Circulation Research; 131:42-58. 

•A Junaid,...., JM van Gils,...., AJ van Zonneveld (2021)  A Microfluidics-Based Screening Tool to Assess the Impact of Blood Plasma Factors on Microvascular Integrity. Adv Biol; 2021; doi:10.1002/adbi.202100954 

• D Vreeken ,...., JM van Gils (2021) Downregulation of Endothelial Plexin A4 Under Inflammatory Conditions Impairs Vascular Integrity . Front Cardiovascular Med ; 2021; doi:10.3389/fcvm.2021.633609 

•H Zhang,...., JM van Gils(2021) Netrin-4 expression by human endothelial cells inhibits endothelial inflammation and senescence. Int J Biochem Cell Biol; 2021; doi:10.1016/j.biocel.2021.105960 

•H Zhang,...., JMV Gils(2021) Comprehensive analysis of neuronal guidance cue expression regulation during monocyte-to-macrophage differentiation reveals post-transcriptional regulation of semaphorin7A by the RNA-binding protein quaking. Innate Immun; 2021; doi:10.1177/1753425920966645 

•H Zhang,...., JM van Gils(2020) Prediction Power on Cardiovascular Disease of Neuroimmune Guidance Cues Expression by Peripheral Blood Monocytes Determined by Machine-Learning Methods. Int J Mol Sci; 2020; doi:10.3390/ijms21176364 

• D Vreeken ,...., JM van Gils (2020) Ephs and Ephrins in Adult Endothelial Biology . Int J Mol Sci ; 2020; doi:10.3390/ijms21165623 

•D Vreeken ,...., JM van Gils(2020) EPH receptor B2 stimulates human monocyte adhesion and migration independently of its EphrinB ligands. J Leukoc Biol; 2020; doi:10.1002/JLB.2A0320-283RR 

•H Zhang,...., JM van Gils(2020) Endothelial Semaphorin 3F Maintains Endothelial Barrier Function and Inhibits Monocyte Migration. Int J Mol Sci; 2020; doi:10.3390/ijms21041471