Investigating the Role of STING in Response to Cardiovascular Inflammation

by Sophia Boxerman

mentor: Alcide Pilar, Immunology, TUMS; funding source: Nathan Gantcher Student Summer Scholars Fund

Sophia-Boxerman-poster

Cardiovascular disease (CVD), claiming 647,000 American lives annually1, is the primary cause of death in the United States. By the end of the year, it is predicted to result in the death of over 2.5 times more Americans than COVID-192. Often correlated with CVD is Peripheral Artery Disease (PAD), a condition involving clogged or stiffened blood vessels in the arms or legs that, in severe cases, precipitates dangerous blood clotting. The effects of PAD can be mitigated through stent angioplasty, the wire-mediated insertion of a mesh-metal tube into the clogged vessel to hold it open indefinitely. Unfortunately, this procedure, though life-saving, results in inevitable, long-term artery damage that impacts vessel health and function years after stent implantation.

The immune-signaling molecule Stimulator of Interferon Genes (STING) has previously been studied as a key mediator of vascular inflammation in STING-associated vasculopathy (SAVI)3.  In this study, we investigated its role in endothelial cells lining blood vessels in response to vascular injury. We hypothesized that STING activating type I interferon genes and modulating a pro-inflammatory response is critical after sensing cellular damage upon injury. To test this hypothesis, we used a mouse model of angioplasty and employed the deposition of elastin— an extracellular matrix protein indicative, in large quantities, of vessel stiffening— as a measure of vessel remodeling.

In this pilot study, both WT and STING-/- mice were subjected to unilateral wire carotid injury and sacrificed 7 or 14 days post-injury to evaluate the dynamic vessel healing response. Injured and contralateral uninjured arteries were isolated, cut into small sections, and stained for elastin. Elastin deposition in these arterial sections was then quantified using ImageJ software.

Our results demonstrate that without an injury stimulus, STING does not contribute to elastin deposition in vessels. This preliminary study also showed that elastin area in STING -/- injured arteries is not different from STING -/- uninjured arteries, though more mice are needed to perform statistical analysis. Nevertheless, this similarity trend in elastin deposition could suggest that vascular STING may contribute to sensing wire-mediated injury. 

Experiments evaluating elastin deposition in additional mice are ongoing. Future in vitro experiments using live cell microscopy studies will be used to translate these in vivo observations into mechanistic findings.

Better understanding the role of STING signaling in blood vessel remodeling post-angioplasty will help doctors treat patients with PAD while minimizing long term side effects by pharmacologically and locally adjusting vascular STING signaling through drug eluting stents and by reducing the long-term post-angioplasty vessel inflammation and stiffening currently observed in patients. 

1CDC. 2020. “Heart Disease Facts | cdc.gov.” Centers for Disease Control and Prevention. https://www.cdc.gov/heartdisease/facts.htm.

2McAndrew T. 2020. University of Massachusetts Amherset. “COVID19-Survey 12-2020-05-04”. http://works.bepress.com/mcandrew/9/.

3 Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Montealegre Sanchez GA, Tenbrock K, Wittkowski H, Jones OY, Kuehn HS et al. (2014). Activated STING in a Vascular and Pulmonary Syndrome. New England Journal of Medicine, 371(6): 507–518. DOI: 10.1056/NEJMoa1312625

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4 thoughts on “Investigating the Role of STING in Response to Cardiovascular Inflammation

  • October 23, 2020 at 4:17 pm
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    Hi Sophia! I really appreciate the clarity of your writing and the applicability of your in vivo experiments. The figures and images you include also really help to communicate your research, very well done!

  • October 23, 2020 at 4:38 pm
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    Hi Sophia, this is a great poster! The connection between your research and pathology is really clear and the methods section on your poster very effectively communicates what you did to investigate your research question. Also, the way your graphs are presented is simple and concise. Best of luck with the future in vitro studies!

  • October 23, 2020 at 4:52 pm
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    Really agree on the clarity! As a decidedly non-STEM person, I was able to make a lot of sense of this. The images really did help. It is nice to be able to really understand what you did!

  • October 23, 2020 at 9:47 pm
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    ^^^100% agree with John. The images and you commentary/explanations make it easy for someone without a STEM background to understand. This is really cool work!

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