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Updated: Feb 3, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Receptor tyrosine kinase profiling of ischemic heart identifies ROR1 as a potential therapeutic target
Juho Heliste1,2,3, Anne Jokilammi1, Ilkka Paatero1,4
1Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520, Turku, Finland.
Background:
Receptor tyrosine kinases (RTK) are potential targets for the treatment of ischemic heart disease. The human RTK family consists of 55 members, most of which have not yet been characterized for expression or activity in the ischemic heart.
Methods:
RTK gene expression was analyzed from human heart samples representing healthy tissue, acute myocardial infarction or ischemic cardiomyopathy. As an experimental model, pig heart with ischemia-reperfusion injury, caused by cardiopulmonary bypass, was used, from which phosphorylation status of RTKs was assessed with a phospho-RTK array. Expression and function of one RTK, ROR1, was further validated in pig tissue samples, and in HL-1 cardiomyocytes and H9c2 cardiomyoblasts, exposed to hypoxia and reoxygenation. ROR1 protein level was analyzed by Western blotting. Cell viability after ROR1 siRNA knockdown or activation with Wnt-5a ligand was assessed by MTT assays.
Results:
In addition to previously characterized RTKs, a group of novel active and regulated RTKs was detected in the ischemic heart. ROR1 was the most significantly upregulated RTK in human ischemic cardiomyopathy. However, ROR1 phosphorylation was suppressed in the pig model of ischemia-reperfusion and ROR1 phosphorylation and expression were down-regulated in HL-1 cardiomyocytes subjected to short-term hypoxia in vitro. ROR1 expression in the pig heart was confirmed on protein and mRNA level. Functionally, ROR1 activity was associated with reduced viability of HL-1 cardiomyocytes in both normoxia and during hypoxia-reoxygenation.
Conclusions:
Several novel RTKs were found to be regulated in expression or activity in ischemic heart. ROR1 was one of the most significantly regulated RTKs. The in vitro findings suggest a role for ROR1 as a potential target for the treatment of ischemic heart injury.
Insights
Novel receptor tyrosine kinases (RTKs) are regulated in ischemic heart disease. ROR1, a receptor tyrosine kinase, shows potential as a therapeutic target for ischemic heart injury.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Oncology
Background:
- Receptor tyrosine kinases (RTKs) are critical signaling molecules with implications in various diseases.
- The role of most RTKs in ischemic heart disease remains largely uncharacterized.
- Understanding RTK expression and activity in the ischemic heart is crucial for identifying therapeutic targets.
Purpose of the Study:
- To investigate the expression and activity of RTKs in human ischemic heart disease.
- To identify novel RTKs regulated by ischemia-reperfusion injury.
- To evaluate the functional role of ROR1 in cardiac cells under stress conditions.
Main Methods:
- RTK gene expression analysis in human heart tissues (healthy, myocardial infarction, ischemic cardiomyopathy).
- Phospho-RTK array analysis in a pig model of ischemia-reperfusion injury.
- Validation of ROR1 expression and function in pig heart, HL-1 cardiomyocytes, and H9c2 cardiomyoblasts under hypoxia-reoxygenation.
- Assessment of cell viability using MTT assays after ROR1 modulation.
Main Results:
- A subset of novel RTKs were found to be actively regulated in the ischemic heart.
- ROR1 exhibited significant upregulation in human ischemic cardiomyopathy.
- ROR1 phosphorylation was suppressed in the pig ischemia-reperfusion model, and its expression decreased in cardiomyocytes under hypoxia.
- ROR1 activity was linked to reduced cardiomyocyte viability during normoxia and hypoxia-reoxygenation.
Conclusions:
- Several novel RTKs are regulated in expression or activity within the ischemic heart.
- ROR1 is a significantly regulated RTK in ischemic heart conditions.
- In vitro findings suggest ROR1 as a potential therapeutic target for treating ischemic heart injury.
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