# Immune Cell Interactions in Atherosclerosis

> **NIH NIH P01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $2,577,670

## Abstract

ABSTRACT
 In the past decade, several groups, including our own, have shown the importance of immune cell subsets
on atherogenesis in mice, but we are just beginning to discover how immune cells are metabolically and
transcriptionally changed during atherogenesis in humans. This PPG will focus on human cardiovascular
disease, and will test the hypothesis that lipoproteins with their lipid and protein components trigger innate and
adaptive immune responses that impact atherosclerosis. We will study functional changes in immune cells and
the immune cell cross-talk that occurs during atherosclerosis progression in humans using the well-
characterized NHLBI-sponsored longitudinal clinical cohort, Multi-Ethnic Study of Atherosclerosis (MESA), and
our UVA Cardiovascular Cohort. We will study subjects who have low versus high cardiovascular risk based on
their coronary artery calcium (CAC) Agatston scores. CAC Agatston scores have high positive predictive
values for cardiovascular disease (CAD) events, and Agatston scores (above 300) are strong predictors of
future CAD events. We will study subjects with CAC Agatston scores >300 as high risk, and we have carefully
matched controls by age and gender with Agatston scores of zero as low risk. In this synergistic program,
Project 1 Monocyte Subsets & Immunity in Mouse and Human Atherosclerosis, will study how monocyte
subsets respond to oxidized LDL to impact cardiovascular disease. Project 2 Cholesterol Regulation of
Inflammatory Macrophages in Atherosclerosis, will investigate how cholesterol modulates macrophage
polarization in atherosclerosis. Project 3 B Cell Subsets in Mouse and Human Atherosclerosis, will study how
specific chemokine receptors promote B cell subset migration and atheroprotection. Project 4 ApoB-Specific
CD4 T cells in Mouse and Human Atherosclerosis, will test the hypothesis that apoB-specific CD4 T cells are
atheroprotective by producing IL-10, but fail later in disease. An important synergistic aspect to our PPG is that
B cells, T cells, monocytes and macrophages communicate with each other in the artery wall and lymphoid
tissues, and each project studies one of these immune cell subsets, so there are many project interactions.
Unique aspects of our program are the strong focus on studying human immune cells, the use of CyTOF mass
cytometry and RNA-Seq as innovative methodologies used to study these cells, the measurement of plasma
immunoglobulins using ELISA-based assays developed in our group and currently used in multiple clinical
trials, and our ability to link all of our group's discoveries with a 15-year extensive MESA clinical database to
understand how immune cells change to contribute to CAC progression and cardiovascular disease. The end
goal of our studies is to identify novel therapeutic strategies targeting immune cell function to limit
cardiovascular disease.

## Key facts

- **NIH application ID:** 9940762
- **Project number:** 5P01HL136275-04
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Catherine C Hedrick
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,577,670
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9940762

## Citation

> US National Institutes of Health, RePORTER application 9940762, Immune Cell Interactions in Atherosclerosis (5P01HL136275-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9940762. Licensed CC0.

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