Human monocyte subsets exhibit divergent angiotensin I-converting activity

Area of Science:

• Immunology
• Cardiovascular Physiology
• Molecular Biology

Background:

• The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating vascular tone and blood pressure.
• Immune cells, specifically monocytes (MO), are increasingly recognized for their potential role within the RAAS.

Purpose of the Study:

• To investigate the expression and activity of angiotensin-converting enzyme type 1 (ACE1) and ACE2 in human monocytes and their subsets.
• To elucidate the role of monocyte subsets in RAAS-mediated vascular homeostasis.

Main Methods:

• Analysis of ACE1 and ACE2 mRNA and protein expression in human monocyte subsets (classical and non-classical).
• In vitro assessment of angiotensin II (Ang II), Ang-(1-9), and Ang-(1-7) generation by monocytes.
• Comparison of enzyme activity across different monocyte populations and peripheral blood mononuclear cells (PBMC).

Main Results:

• Classical monocytes (CD14(++)CD16(-)) exhibited the highest ACE1 and ACE2 mRNA expression, with ACE2 levels nearly double ACE1.
• ACE1 and ACE2 protein expression was most prominent in monocytes and classical monocytes within PBMC.
• Classical monocytes showed the highest Ang II generation, while non-classical monocytes (CD14(+)CD16(++)) produced significantly more vasoprotective Ang-(1-7) than Ang II.

Conclusions:

• Human monocytes, especially classical and non-classical subsets, are involved in RAAS-related mechanisms that may regulate vascular homeostasis.
• Non-classical monocytes display a vasoprotective phenotype, potentially through enhanced Ang-(1-7) formation, and are associated with the vascular endothelium.