Receptor tyrosine kinase profiling of ischemic heart identifies ROR1 as a potential therapeutic target

• DOI: 10.1186/s12872-018-0933-y
• Publication Date: 2018-10-20T13:03:42Z
• Authors: Juho Heliste; Anne Jokilammi; Ilkka Paatero; Deepankar Chakrob...; Christoffer Stark; Timo Savunen; Maria Laaksonen; Klaus Elenius
• Keywords: Angiology; ROR1; Profiling (computer programming)

Receptor tyrosine kinases (RTK) are potential targets for the treatment of ischemic heart disease. The human RTK family consists 55 members, most which have not yet been characterized expression or activity in heart. gene was analyzed from samples representing healthy tissue, acute myocardial infarction cardiomyopathy. As an experimental model, pig with ischemia-reperfusion injury, caused by cardiopulmonary bypass, used, phosphorylation status RTKs assessed a phospho-RTK array. Expression and function one RTK, ROR1, further validated tissue samples, HL-1 cardiomyocytes H9c2 cardiomyoblasts, exposed to hypoxia reoxygenation. ROR1 protein level Western blotting. Cell viability after siRNA knockdown activation Wnt-5a ligand MTT assays. In addition previously RTKs, group novel active regulated detected significantly upregulated However, suppressed model were down-regulated subjected short-term vitro. confirmed on mRNA level. Functionally, associated reduced both normoxia during hypoxia-reoxygenation. Several found be RTKs. vitro findings suggest role as target injury.