KLF6 mediated mechanism as a therapeutic target in aortic diseases

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Previous studies suggest that Kruppel-like factors (KLFs) play important roles in the cardiovasculature. Preliminary studies indicated that KLF6 have roles in cardiovascular development and remodeling such as cardiac fibrosis. In this study, we next aimed to decipher the mechanism in which KLF6 mediates aortic pathologies such as aortic aneurysm or dissection. Continuous angiotensin II (AngII) infusion in klf6+/- mice resulted in decreased TGFbeta-1 expression levels both in aortic wall and serum in KLF6+/- mice, and diminished blood pressure increase (wild-type 150-160 mmHg, KLF6+/- 100-120 mmHg), which indicates possibility of blood pressure control gy KLF6 inhibition. On the other hand, KLF6+/ mice showed accelerated aortic remodeling such as inflammatory cell infiltration or MMP-2 induction and aortic walldestruction in aortic aneurysm/dissection formation with AngII + Cacl2. These data collectively showed the biphasic mechanism in aortic pathologies, indicating the importanc of meticulous decision of KLF6 targeting therapies.