# MICROVASCULAR MECHANISMS OF ARTICULAR DAMAGE IN ANTIGEN

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 1991 · $61,270

## Abstract

The overall goal of this proposal is to determine whether microvascular
injury is a major determinant of articular destruction in immune mediated
arthritis.  We hypothesize that microvascular injury in immune mediated
arthritis leads to ischemia and damage to intra-articular structures and
subchondral (subarticular) bone.  Using an animal model of immune-
mediated arthritis, the Dumonde Glynn model of antigen induced arthritis
(AIA), we will apply new methods of microperfusions to study microvessel
occlusion and proliferation during the development of acute AIA and
during the evolution of chronic erosive AIA; Using tissue clearance
methods we will measure the changes in articular blood flow in acute and
chronic AIA which can be correlated with changes in microvessel
morphology; Using radiotracer labeled microsperes, distribution of
articular blood flow to the individual intra-articular components and
epiphyseal bone will be measured in acute and chronic AIA.

The second main focus of this project is to investigate the effects of
modulating angiogenesis on the development of articular damage during
acute and chronic AIA.  We will measure the changes in articular blood
flow, blood flow distribution, microvessel morphology and histopathology
of acute and chronic AIA in control and three treatment groups of
animals; We will measure the effects in these experimental groups:  1)
AIA rabbits anticoagulated with oral coumadin to examine the effects of
blocking the initial microvascular occlusion in immune mediated
synovitis.  2) AIA rabbits treated with oral heparin to enhance
angiogenesis; and 3) AIA rabbits treated with oral heparin plus
hydrocortisone or the non-glucocorticoid, epicortisol to inhibit
angiogenesis.  If angiogenesis plays a pathogenic role in the erosive
process of antigen induced arthritis, enhancement of angiogenesis will
increase the severity of AIA and inhibition of angiogenesis will abrogate
or lessen the severity of AIA.

Chronic inflammatory arthritis produces non-reversible joint destruction
in two to seven million individuals in the USA.  Its cause and hence
specific treatment are unknown and produces health care costs which are
three times the national average health care costs.  Demonstration of the
microvascular injury hypothesis and demonstration of decreased joint
destruction by angiomodulation will lead to novel avenues for therapeutic
intervention designed to prevent ultimate joint destruction.

## Key facts

- **NIH application ID:** 3159114
- **Project number:** 5R01AR039148-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **SAM.gov UEI:** KABJZBBJ4B54
- **Principal Investigator:** Maren Lawson Mahowald
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $61,270
- **Award type:** 5
- **Project period:** 1989-09-30 → 1993-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159114

## Citation

> US National Institutes of Health, RePORTER application 3159114, MICROVASCULAR MECHANISMS OF ARTICULAR DAMAGE IN ANTIGEN (5R01AR039148-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159114. Licensed CC0.

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