# Role of Myeloid Cells in Cerebrovascular Permeability and Reactivity in Older HIV Infected Individuals

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $696,405

## Abstract

HIV infected individuals, especially those older, are at increased risk of developing cerebrovascular disease
(CBVD). While most of the recent investigations have focused on large vessel disease, cerebral small vessel
disease (CSVD) has received much less attention despite its known role and long-term effect on cognitive
performance and potentially more direct link to HIV-associated immune dysregulation. CSVD is diagnosed via
neuroimaging. Typical findings include small subcortical infarcts, lacunes, white matter hyperintensity, enlarged
perivascular spaces, cerebral microbleeds and brain atrophy. Quantitative MR techniques assess indirectly the
altered microcirculation and blood brain barrier (BBB) by measuring vascular reactivity, cerebral blood flow,
white matter microstructure and tissue susceptibility. Importantly, these quantitative imaging modalities can
measure even subtle brain abnormalities that escape the evaluation by standard clinical imaging techniques.
 CSVD has been associated with markers secreted by myeloid cells. This is particularly relevant to HIV
infected individuals. We and others have shown that the aberrant platelet activation during HIV/SIV infection
causes an increase in platelet-monocyte complexes (PMCs) that drives monocyte maturation from
CD14+/CD16- to the pro-inflammatory CD14(low)/CD16+ phenotype and that the reduced numbers of
CD14+/CD16- monocytes are associated with pro-AS changes, BBB permeability and aging. Thus, PMCs
could serve as markers and a therapeutic target of CSVD. Based on these observations, we hypothesize that
PMCs, by affecting vascular permeability and reactivity, play a crucial role in mediating CSVD, especially in
older HIV infected individuals.
 In a well characterize cohort for CBVD risk factors that includes an older-enriched HIV population (age≥50)
and age matched uninfected individuals, we propose to address the following Specific Aims pertinent to CSVD
in a 3-year longitudinal study. In Aim 1 we will assess whether changes in vascular reactivity (measured via
rs-fMRI) and white matter microstructural integrity (measured via DTI) are associated with levels of PMCs. In
Sub-Aim 1 we will determine whether areas with increased tissue susceptibility and decreased vascular
reactivity are associated with decreased cerebral blood flow (CBF). In Aim 2 we will determine whether
changes vascular reactivity and white matter microstructural integrity are associated with soluble products of
pro-inflammatory monocytes (plasma levels of sCD163, neopterin, and HMGB1), platelet activation (platelet
factor 4 [PF-4]) and with plasma markers of endothelial dysfunction (intercellular adhesion molecule 1 [sICAM-
1], vascular cellular adhesion molecule-1 [sVCAM-1], osteoprotegerin and lipoprotein-associated
phospholipase A2 [Lp-PLA2] mass). In Sub-Aim 2 we will determine whether changes in brain iron deposition
are associated with levels of PMCs, PF-4, plasma monocyte and endothelial soluble products.
 In Aim 3...

## Key facts

- **NIH application ID:** 10160749
- **Project number:** 5R01AG054328-05
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** SANJAY B. MAGGIRWAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $696,405
- **Award type:** 5
- **Project period:** 2017-07-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160749

## Citation

> US National Institutes of Health, RePORTER application 10160749, Role of Myeloid Cells in Cerebrovascular Permeability and Reactivity in Older HIV Infected Individuals (5R01AG054328-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10160749. Licensed CC0.

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