DIZE's Anti-Fibrotic Effect Works Through Cardiomyocytes, Not Fibroblasts
- Co-culture and transcriptomics indicate that diminazene aceturate activates ACE2 on cardiomyocytes, raising Ang-(1–7), which then suppresses TGF-β signalling in neighbouring fibroblasts; the Ang-(1–7) antagonist A779 partly reversed this.
- A collagen-binding, focused-ultrasound-responsive nanoplatform delivered DIZE to the infarct in rats.
- The release improved cardiac function and reduced fibrosis, with restored ACE2/Ang-(1–7) signalling.
💡 Points Based on the abstract
DIZE's status as an ACE2 'agonist' has long been contested and it is an antiparasitic with other activities, so the partial A779 block leaves real room for off-ACE2 effects; an ACE2-knockout or cardiomyocyte-specific control would settle it. The delivery platform is clever but adds a device-dependent step; the question for translation is whether a better-characterised ACE2 activator could be dosed without the ultrasound.
📄 Paper · Biochemical Pharmacology ↗ Cardiomyocyte-derived ACE2/Ang-(1–7) axis mediates DIZE-induced inhibition of TGF-β signaling to attenuate cardiac fibrosis following myocardial infarction