# Myeloperoxidase, Chronic Kidney Disease and Atherosclerosis

> **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $47,520

## Abstract

Project Summary/Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in chronic kidney disease (CKD),
reducing the life expectancy of CKD and dialysis patients to roughly half to one-third that of the general
population. However, the pathogenesis of the accelerated CVD in CKD is not yet clearly understood, and no
specific therapeutic strategies are currently available to attenuate this phenomenon. Our long-term goal is to
understand the mechanisms underlying accelerated atherosclerosis in order to develop diagnostic and
therapeutic solutions to improve the lifespan of patients with CKD. Our overall objective is to define the role of
myeloperoxidase in the pathophysiology of CKD atherosclerosis. Our central hypothesis is that the
myeloperoxidase oxidized HDL accelerates cardiovascular disease in CKD. Our rationale is that if
myeloperoxidase oxidized HDL accelerates CKD atherosclerosis, then we can develop new therapeutic
strategies and biomarkers to attenuate the CVD burden in the CKD population. We will test our central
hypothesis by demonstrating the role of myeloperoxidase oxidation on the efflux capacity, HDL proteome, and
incident CVD events in CKD patients. We will delineate the extent of myeloperoxidase-based oxidation of HDL
using mass spectrometry in 348 patients of the RRI-CKD and test their ability to predict CVD events. We also
evaluate the effect of myeloperoxidase oxidized HDL on cholesterol efflux capacity and the HDL proteome.
This project was delayed by the multiple lab closures and core staff delays caused by the COVID-19
pandemic. Support from the NHLBI for continued protected time and salary will ensure this project's completion
and help establish Dr. Mathew's research independence. The proposed research is innovative in that it links
myeloperoxidase oxidation of the HDL proteome to accelerated CVD in CKD via mass spectrometric metabolic
profiling and HDL proteomics. The proposed research is significant because it will provide strong evidence of
the role of myeloperoxidase oxidized HDL in the pathogenesis and prediction of CVD in CKD patients,
potentially leading to clinical studies to prevent CV events in CKD atherosclerosis.

## Key facts

- **NIH application ID:** 10390888
- **Project number:** 3K08HL130944-05S1
- **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:** 2021
- **Award amount:** $47,520
- **Award type:** 3
- **Project period:** 2016-09-01 → 2022-01-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390888

## Citation

> US National Institutes of Health, RePORTER application 10390888, Myeloperoxidase, Chronic Kidney Disease and Atherosclerosis (3K08HL130944-05S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10390888. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*