# Myeloperoxidase, Chronic Kidney Disease and Atherosclerosis

> **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $169,480

## Abstract

ABSTRACT
 There is a worldwide increase in the incidence and prevalence of chronic kidney disease (CKD) affecting
~11% of adults in the U.S. CKD is a risk factor for CAD, as CKD patients have CAD prevalence of nearly 40%
and greater than 10-fold mortality compared to healthy controls. Traditional risk factors are only partially
predictive of CAD in CKD subjects, highlighting the need for mechanism-based novel biomarkers that can
accurately stratify CAD risk in CKD patients. This proposal directly addresses this critical gap in our diagnostic
and prognostic capabilities. We will explore the relationship between CKD, oxidative stress and atherosclerosis
in a physiologically relevant animal model with complementary human studies. Evidence strongly implicate a
central role for oxidative stress in atherosclerosis but its role in the initiation and progression of CKD-
accelerated atherosclerosis has not been systematically investigated. One well-characterized source of
oxidative stress is myeloperoxidase (MPO), a heme enzyme that co-localizes with macrophages in human
atherosclerotic lesions. While previous studies have attributed MPO oxidation playing a leading role in
atherosclerosis, its role in CKD-atherosclerosis has not been systematically elucidated. The overall goals of
this proposal are to investigate whether MPO promotes atherogenic risk in CKD. Preliminary studies in a
mouse model of CKD strongly demonstrated that MPO oxidative pathway is upregulated in CKD and
associated with accelerated atherosclerosis. These observations form the basis of the proposal in which we
will test the hypothesis that modulating MPO levels will alter CKD related atherosclerosis in vivo. Together with
complementary human studies, we will systematically assess the role of MPO in CKD-accelerated
atherosclerosis.
 The proposed experiments and training plan will enable the PI to gain in depth understanding in cutting
edge mass spectrometry and proteomic technologies coupled with intense exposure to vascular biology,
transgenic mouse models and clinical research methodology. Specific aims
 1) Investigate if MPO plays a central role in CKD-accelerated atherosclerosis mouse models
 2) Determine the role of MPO oxidation and lipoprotein profiles in CKD patients with and without CAD
 These studies will provide evidence for a crucial role for MPO oxidation in the initiation and progression of
atherosclerosis in CKD and would facilitate the rational design of interventions to interrupt MPO oxidation.

## Key facts

- **NIH application ID:** 10001572
- **Project number:** 5K08HL130944-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Anna Vachaparampil Mathew
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $169,480
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-01-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001572

## Citation

> US National Institutes of Health, RePORTER application 10001572, Myeloperoxidase, Chronic Kidney Disease and Atherosclerosis (5K08HL130944-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10001572. Licensed CC0.

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