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ACE Overexpression in Myelomonocytic Cells: Effect on a Mouse Model of Alzheimer’s Disease

  • Hypertension and the Kidney (R Carey, Section Editor)
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Abstract

While it is well known that angiotensin converting enzyme (ACE) plays an important role in blood pressure control, ACE also has effects on renal function, hematopoiesis, reproduction, and aspects of the immune response. ACE 10/10 mice overexpress ACE in myelomonocytic cells. Macrophages from these mice have an increased polarization towards a pro-inflammatory phenotype that results in a very effective immune response to challenge by tumors or bacterial infection. In a mouse model of Alzheimer’s disease (AD), the ACE 10/10 phenotype provides significant protection against AD pathology, including reduced inflammation, reduced burden of the neurotoxic amyloid-β protein and preserved cognitive function. Taken together, these studies show that increased myelomonocytic ACE expression in mice alters the immune response to better defend against many different types of pathologic insult, including the cognitive decline observed in an animal model of AD.

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Acknowledgment

The authors acknowledge the tireless support of Mr. Brian Taylor. This study was supported by the National Institute of Health grants R01 HL110353 (KEB) and R00 HL088000 (RAG-V); Beginning Grant-in-Aid 13BGIA14680069 (XZS) and Scientist Development Grant 11SDG6770006 (PDS) from the American Heart Association; the Coins for Alzheimer's Research Trust (C.A.R.T) Fund (MK-H); the BrightFocus Foundation (MK-H), the Maurice Marciano Family Foundation (MK-H), and by the National Center for Advancing Translational Sciences through CTSI Grant UL1TR000124 (MK-H).

Compliance with Ethics Guidelines

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Conflict of Interest

Yosef Koronyo, Ellen Bernstein, Jorge F. Giani, Tea Janjulia, Keith L. Black, and Sebastien Fuchs declare that they have no conflict of interest.

Maya Koronyo-Hamaoui has received grants from the Coins for Alzheimer's Research Trust (C.A.R.T) Fund, The BrightFocus Foundation, and The Maurice Marciano Family Foundation, along with travel support from The Coins for Alzheimer's Research Trust (C.A.R.T) Fund. She also has pending grants from The Coins for Alzheimer's Research Trust (C.A.R.T) Fund, The BrightFocus Foundation, and The Maurice Marciano Family Foundation.

Kandarp Shah has received a grant from the NIH.

Peng D. Shi has received a grant from the American Heart Association.

Romer A. Gonzalez-Villalobos has received a grant from the NIH.

Xiao Z. Shen has received a grant from the American Heart Association.

Kenneth E. Bernstein has received a grant from the NIH.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Neurosurgery and the Maxine Dunitz Neurosurgical Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

    Maya Koronyo-Hamaoui, Yosef Koronyo & Keith L. Black

  2. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

    Maya Koronyo-Hamaoui, Kandarp Shah, Ellen Bernstein, Jorge F. Giani, Tea Janjulia, Romer A. Gonzalez-Villalobos, Sebastien Fuchs, Xiao Z. Shen & Kenneth E. Bernstein

  3. Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

    Peng D. Shi

  4. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

    Romer A. Gonzalez-Villalobos, Sebastien Fuchs, Xiao Z. Shen & Kenneth E. Bernstein

  5. Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA, 91766, USA

    Sebastien Fuchs

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  1. Maya Koronyo-Hamaoui
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  2. Kandarp Shah
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Correspondence to Kenneth E. Bernstein.

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This article is part of the Topical Collection on Hypertension and the Kidney

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Koronyo-Hamaoui, M., Shah, K., Koronyo, Y. et al. ACE Overexpression in Myelomonocytic Cells: Effect on a Mouse Model of Alzheimer’s Disease. Curr Hypertens Rep 16, 444 (2014). https://doi.org/10.1007/s11906-014-0444-x

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