# Mechanistic basis of sexual dimorphism in antigen-independent IgG1 angiogenesis regulation

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $651,084

## Abstract

PROJECT ABSTRACT/SUMMARY
Diseases of excess, aberrant, or insufficient angiogenesis are responsible for a large portion of the world's
morbidity and mortality. Conditions such as peripheral artery disease, macular degeneration, coronary artery
disease, stroke, and heart failure exhibit sexual dimorphism in risk factors, prevalence, severity, or optimal
interventions. Despite widespread appreciation of these differences, the mechanisms by which sex influences
vascular conditions are incompletely understood. For example, the role of sex chromosomal complement in
angiogenic processes is ill defined. New evidence suggests that the process by which IgG1 antibodies regulate
angiogenesis in an antigen-independent manner (which we term “antibody-dependent cell-mediated
angioinhibition” or ADCAI) is strongly sexually dimorphic, with males exhibiting far greater ADCAI compared to
females. Supported by robust preliminary data, the overall hypothesis of this project is ADCAI dimorphism arises
due to expression of the Y chromosome-encoded gene DDX3Y. We will test this hypothesis in three specific
aims. 1) We will establish the precise roles of sex-biasing factors (sex chromosome complement and gonadal
secretions) in ADCAI sexual dimorphism. 2) We will determine the function of the Y chromosome-encoded
DDX3Y as a novel ADCAI regulatory gene. 3) We will quantify the sex effect on ADCAI in human cells and
specimens. Collectively, these thematically related, but independent aims will establish new foundational and
translationally relevant knowledge about the mediators and consequences of ADCAI. These studies may thereby
open new interventional avenues to modulate angiogenesis in a personalized, sex-specific manner for diverse
therapeutic applications.

## Key facts

- **NIH application ID:** 10817893
- **Project number:** 5R01HL164592-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Bradley David Gelfand
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $651,084
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817893

## Citation

> US National Institutes of Health, RePORTER application 10817893, Mechanistic basis of sexual dimorphism in antigen-independent IgG1 angiogenesis regulation (5R01HL164592-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10817893. Licensed CC0.

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