# Serum Amyloid as a Critical mediator between inflammation and thrombosis

> **NIH VA I01** · CENTRAL ARKANSAS VETERANS HLTHCARE SYS · 2020 · —

## Abstract

Acute and chronic inflammation contributes significantly to poor health, most notably as a risk factor for
the development of atherosclerotic vascular disease and its complications, such as myocardial
infarction/acute coronary syndromes (ACS), strokes, and limb ischemia. The medical costs associated
with atherosclerosis contribute to preventable death and serious disability, which strain the VA health
care system. Despite the well-established relationship between inflammation, atherosclerotic disease
and ACS, treatment strategies are limited, due in part to a lack of understanding of the mechanism(s)
by which inflammation stimulates thrombosis. The ability of statin therapy to lower ACS in patients with
elevated C-reactive protein and the recent results from the CANTOS trial suggest that it may be
possible to prevent arterial thrombosis by targeting inflammation. A better understanding of the
inflammatory signals that contribute to acute thrombosis could provide a more precise strategy for
future interventions. In this proposal, we provide evidence that the acute phase reactant serum amyloid
A (SAA) has direct effects on platelet function. SAA levels increase dramatically with acute
inflammation and myocardial injury and are modestly elevated with chronic inflammation. Based on our
findings, we suggest the central hypothesis that SAA serves as a key link between inflammation and
thrombosis. To test this hypothesis, we have assembled an exceptional group of VA investigators with
complimentary expertise in inflammation and thrombosis and unique model systems and reagents.
Importantly, we have “gain” and “loss” of function animal models in which SAA levels can be modulated
independent of inflammation and following different inflammatory challenges. We will apply these
resources to accomplish the following two specific aims: (1) to identify the role of SAA in modulating
platelet aggregation and thrombosis and the molecular mechanism(s) involved and (2) to elucidate the
role of SAA in promoting platelet secretion and leukocyte interactions during inflammation. The aims of
this grant provide a vehicle to address a major unresolved issue in the field, namely identification of
specific inflammatory mediators that influence thrombosis through effects on platelet function and the
signaling pathways involved. These results will be significant, because they are expected to provide
innovative targets and provide proof-of-concept for novel inhibitors that may be used for prevention and
treatment for the complications of inflammation in humans.

## Key facts

- **NIH application ID:** 10807568
- **Project number:** 7I01BX004671-02
- **Recipient organization:** CENTRAL ARKANSAS VETERANS HLTHCARE SYS
- **Principal Investigator:** ANDREW J MORRIS
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 7
- **Project period:** 2020-04-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807568

## Citation

> US National Institutes of Health, RePORTER application 10807568, Serum Amyloid as a Critical mediator between inflammation and thrombosis (7I01BX004671-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10807568. Licensed CC0.

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