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Overexpression of ACE in Myeloid Cells Increases Immune Effectiveness and Leads to a New Way of Considering Inflammation in Acute and Chronic Diseases

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Abstract

Purpose of Review

To review recent studies exploring how myeloid cell overexpression of angiotensin-converting enzyme (ACE) affects the immune response and to formulate an approach for considering the effectiveness of inflammation in cardiovascular disease

Recent Findings

While it is widely appreciated that the renin-angiotensin system affects aspects of inflammation through the action of angiotensin II, new studies reveal a previously unknown role of ACE in myeloid cell biology. This was apparent from analysis of two mouse lines genetically modified to overexpress ACE in monocytes/macrophages or neutrophils. Cells overexpressing ACE demonstrated an increased immune response. For example, mice with increased macrophage ACE expression have increased resistance to melanoma, methicillin-resistant Staphylococcus aureus, a mouse model of Alzheimer’s disease, and ApoE-knockout-induced atherosclerosis. These data indicate the profound effect of increasing myeloid cell function. Further, they suggest that an appropriate way to evaluate inflammation in both acute and chronic diseases is to ask whether the inflammatory infiltrate is sufficient to eliminate the immune challenge.

Summary

The expression of ACE by myeloid cells induces a heightened immune response by these cells. The overexpression of ACE is associated with immune function beyond that possible by wild type (WT) myeloid cells. A heightened immune response effectively resolves disease in a variety of acute and chronic models of disease including models of Alzheimer’s disease and atherosclerosis.

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Funding

This work was supported by National Institutes of Health Grants P01HL129941 (K.E.B.), R01AI143599 (K.E.B.), R01HL142672 (J.F.G.), R01AG055865 (M.K.H.), T32DK007770 (L.C.V.), K99HL141638 (DOD), P30DK063491 (J.F.G.), and the American Heart Association (AHA) Grants 17GRNT33661206 (K.E.B.), 16SDG30130015 (J.F.G.), and 19CDA34760010 (Z.K.). M.K.H. is supported by BrightFocus Foundation Award A2013328S00.

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Correspondence to Kenneth E. Bernstein.

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This article is part of the Topical Collection on Inflammation and Cardiovascular Diseases

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Veiras, L.C., Cao, D., Saito, S. et al. Overexpression of ACE in Myeloid Cells Increases Immune Effectiveness and Leads to a New Way of Considering Inflammation in Acute and Chronic Diseases. Curr Hypertens Rep 22, 4 (2020). https://doi.org/10.1007/s11906-019-1008-x

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Keywords

  • Angiotensin-converting enzyme
  • Myeloid cells
  • Macrophage
  • Neutrophil
  • Immunity
  • Atherosclerosis