# Mechanisms linking obesity and abdominal aortic aneurysm

> **NIH VA I01** · VA MEDICAL CENTER - LEXINGTON, KY · 2020 · —

## Abstract

Obesity has emerged as a risk factor for human and angiotensin II (AngII)-induced abdominal aortic
aneurysms (AAA). Obesity is highly prevalent in Veterans; the Veteran population also has high prevalence of
other risk factors for AAAs (male sex, smoking, hypertension). To date, no single therapy has proven effective
to blunt progressive growth of AAAs, likely due to diverse etiologies underlying AAAs in the human population.
Thus, therapies must be individualized to target the relevant risk factor(s), such as obesity and its
mechanisms, to effectively ameliorate AAA initiation and progression. We previously reported that obesity
promotes AngII-induced AAAs in mice through inflammation in the perivascular adipose tissue. We now have
preliminary data demonstrating that whole body deficiency of serum amyloid A (SAA) profoundly reduces
AngII-induced AAAs in the setting of obesity. Moreover, our recently published data demonstrate that SAA
stimulates macrophage secretion of IL-1β, an inflammatory cytokine implicated in both human and AngII-
induced AAAs. In obese subjects, adipocytes become a predominate source of local and systemic SAA. We
propose that AngII, periaortic fat and SAA come together in the setting of obesity to create a pro-inflammatory
environment immediately adjacent to the abdominal aorta which leads to AAA initiation and expansion. The
central hypothesis of this proposal is in the setting of obesity, adipocyte-derived SAA activates the NLRP3
inflammasome in macrophages to promote AAA development in obesity. Aim 1 will test the hypothesis that
adipocyte-derived SAA is central in creating the pro-inflammatory environment that promotes AngII-induced
AAA formation in obesity. In Aim 2, we will test the hypothesis that adipocyte-derived SAA promotes obesity-
induced AAA by activating the NLRP3 inflammasome in macrophages. We have unique mouse models of SAA
deficiency as well as transgenic mice with tissue-specific SAA-overexpression in which we can overexpress
SAA only in liver or only in fat. We will employ translational therapeutic approaches to prevent the formation
and progression of AngII-induced AAAs in obesity. The impact of these studies is that we will identify SAA and
periaortic fat burden as biomarkers and risk factors for AAA development and progression in the obese
population which may identify precision-targeted AAA therapeutics.

## Key facts

- **NIH application ID:** 9974276
- **Project number:** 5I01BX004275-02
- **Recipient organization:** VA MEDICAL CENTER - LEXINGTON, KY
- **Principal Investigator:** LISA R TANNOCK
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974276

## Citation

> US National Institutes of Health, RePORTER application 9974276, Mechanisms linking obesity and abdominal aortic aneurysm (5I01BX004275-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9974276. Licensed CC0.

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