Atherosclerotic cardiovascular diseases continue to be the leading cause of death worldwide. Viral infections, such as SARS-CoV-2, accelerate atherosclerotic plaque progression and increase the incidence of myocardial infarction and strokes. Previous studies indicated that viral infections increase retrotransposon (RT) expression; however, their role in exacerbating the chronic inflammatory state of atherosclerosis has not been explored. USF researchers discovered that increases in RT expression, specifically Alu double stranded RNA, by viral infections exacerbate the inflammatory state of atherosclerosis and increase the risk of plaque rupture. They showed that human lungs and coronary arteries (hCA) isolated from SARS-CoV-2 positive patients exhibited increased expression of Alu RNA as well as inflammasome-associated genes and pro-inflammatory cytokines. These results indicate that Alu RNA plays an important role in inducing the sustained non-resolving inflammation in atherosclerosis. Current studies focus on targeting Alu RNA with novel antisense oligos (ASOs). This potential therapy represents a novel anti-atherosclerotic therapeutic strategy that targets the inflammatory pathway.
Alu RNA induce pro- and anti-inflammatory response - RT-qPCR for the indicated genes normalized to GAPDH in EC treated with 100 nM chaetocin for 16 hrs or transfected with IVT AluSz RNA for 20 hrs. Data represent the mean ± SEM of a representative experiment.