Myeloid ACE2 upregulation protected against sepsis-induced mortality, hypotension, and vascular dysfunction in mice by suppressing oxidative stress and macrophage polarization.
Does myeloid ACE2 upregulation improve mortality, hypotension, and vascular dysfunction in sepsis models?
Myeloid ACE2 protects against sepsis-mediated hypotension and vascular dysfunction via the Ang (1-7)-MasR-NF-κB and STAT1 pathways, suggesting ACE2 upregulation as a potential therapeutic target.
Angiotensin converting enzyme 2 (ACE2) is a new identified member of the renin-angiotensin-aldosterone system (RAAS) that cleaves angiotensin II (Ang II) to Ang (1-7), which exerts anti-inflammatory and antioxidative activities via binding with Mas receptor (MasR). However, the functional role of ACE2 in sepsis-related hypotension remains unknown. Our results indicated that sepsis significantly reduced blood pressure and led to disruption between ACE-Ang II and ACE2-Ang (1-7) balance. ACE2 knock-in mice exhibited improved sepsis-induced mortality, hypotension and vascular dysfunction, while ACE2 knockout mice exhibited the opposite effects. Bone marrow transplantation and in vitro experiments confirmed that myeloid ACE2 exerted a protective role by suppressing oxidative stress, NO production and macrophage polarization via the Ang (1-7)-MasR-NF-κB and STAT1 pathways. Thus, ACE2 on myeloid cells could protect against sepsis-mediated hypotension and vascular dysfunction, and upregulating ACE2 may represent a promising therapeutic option for septic patients with hypotension.
Li et al. (Tue,) conducted a other in Sepsis-related hypotension. ACE2 knock-in / upregulation vs. ACE2 knockout / control was evaluated on Sepsis-induced mortality, hypotension and vascular dysfunction. Myeloid ACE2 upregulation protected against sepsis-induced mortality, hypotension, and vascular dysfunction in mice by suppressing oxidative stress and macrophage polarization.