Ilakya Selvarajan, Miika Kiema, Ru-Ting Huang, Jin Li, Jiayu Zhu, Petri Pölönen, Tiit Örd, Kadri Õunap, Mehvash Godiwala, Anna Kathryn Golebiewski, Aarthi Ravindran, Kiira Mäklin, Anu Toropainen, Lindsey K Stolze, Maximiliano Arce, Peetra U Magnusson, Stephen White, Casey E Romanoski, Merja Heinäniemi, Johanna P Laakkonen, Yun Fang, Minna Kaikkonen-Määttä
BACKGROUND: CALCRL (calcitonin receptor-like) protein is an important mediator of the endothelial fluid shear stress response, which is associated with the genetic risk of coronary artery disease. In this study, we functionally characterized the noncoding regulatory elements carrying coronary artery disease that risks single-nucleotide polymorphisms and studied their role in the regulation of CALCRL expression in endothelial cells. METHODS: To functionally characterize the coronary artery disease single-nucleotide polymorphisms harbored around the gene CALCRL , we applied an integrative approach encompassing statistical, transcriptional (RNA-seq), and epigenetic (ATAC-seq, chromatin immunoprecipitation assay-quantitative polymerase chain reaction, and electromobility shift assay) analyses, alongside luciferase reporter assays, and targeted gene and enhancer perturbations (siRNA and clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) in human aortic endothelial cells...
April 11, 2024: Arteriosclerosis, Thrombosis, and Vascular Biology