Novel ACE2-Fc chimeric fusion provides long-lasting hypertension control and organ protection in mouse models of systemic renin angiotensin system activation

摘要: Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that potently degrades angiotensin II to 1-7. Previous studies showed injection of the enzymatic ectodomain recombinant ACE2 (rACE2) markedly increases circulatory levels activity, and effectively lowered blood pressure in II-induced hypertension. However, due short plasma half-life rACE2, its therapeutic potential for chronic use limited. To circumvent this, we generated chimeric fusion rACE2 immunoglobulin fragment Fc segment increase stability. This rACE2-Fc protein retained full peptidase activity exhibited greatly extended mice, from less than two hours original over week. A single 2.5 mg/kg increased overall II-conversion activities by up 100-fold enhanced recovery acute induced hypertension seven days after administration. assess given weekly on cardiac protection, performed mice continuously infused with 28 Renin transgenic mouse model The achieved sustained control reduced hypertrophy fibrosis. In hypertensive injections pressure. Additionally, ameliorated albuminuria, kidney Thus, our strategy suitable future development new renin system-based inhibition therapies.