Inhibition of the multifunctional homeodomain-interacting protein kinase 2 (HIPK2) alleviates thoracic aortic disease in mice with progressively severe Marfan syndrome

Thoracic aortic aneurysm (TAAs) are a severe complication in Marfan Symdrome (MFS), often leading to dissection and premature death. To identify potential drug targets for the treatment for TAAs we used gene expression profiles from MFS mice and patients to predict kinases that regulate gene expression. Among the top predictions was the kinase HIPK2. Ubiquitous post-natal inactivation of the HIPK2 gene, as well as chronic administration of an allosteric inhibitor of HIPK2/Smad3 interaction, increased the survival of MFS mice and improved multiple surrogate parameters. Overall design: The data that was first published with this study, contained 4 samples obtained from both MFS and WT mice and 3 samples obtained from both MFS patients and non-MFS control subjects.