PTEN Inhibitor VO-OHpic Attenuates Inflammatory M1 Macrophages and Cardiac Remodeling in Doxorubicin-Induced Cardiomyopathy.

PTEN Inhibitor VO-OHpic Attenuates Inflammatory M1 Macrophages and Cardiac Remodeling in Doxorubicin-Induced Cardiomyopathy. Am J Physiol Heart Circ Physiol. 2018 Aug 10;: Authors: Johnson TA, Singla DK Abstract Doxorubicin (Doxo) is an effective agent commonly used in cancer therapeutics. Unfortunately, Doxo treatment can stimulate cardiomyopathy and subsequent heart failure, limiting use of this drug. The role of phosphatase and tensin homolog (PTEN) in apoptosis has been documented in Doxo induced cardiomyopathy (DIC) and heart failure models. However, whether direct inhibition of PTEN attenuates apoptosis, cardiac remodeling, and inflammatory M1 macrophages in DIC model remains elusive. Therefore, the current study is designed to understand effects of VO-OHpic (VO), a potent inhibitor of PTEN, in reducing apoptosis and cardiac remodeling. At D56, echocardiography was performed, which shows VO-OHpic treatment significantly (p&lt;0.05) improves heart function. Immunohistochemistry, TUNEL, and histological staining were used to determine apoptosis, pro-inflammatory M1 macrophages, anti-inflammatory M2 macrophages, and cardiac remodeling. Our data shows a significant increase in apoptosis, hypertrophy, fibrosis, and pro-inflammatory M1 macrophages with Doxo treatment, whereas VO treatment significantly reduced apoptosis, adverse cardiac remodeling, and pro-inflammatory M1 macrophages significantly (p<0.05) compared to Doxo gro...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research