Circulating cell-free DNA and its association with cardiovascular disease: what we know and future perspectives

Abstract

Purpose of review The aim of this review is to explore a possible link between cell-free DNA (cfDNA) and cardiovascular disease (CVD), which may hold valuable potential for future diagnostics. Recent findings cfDNA has become topic of high interest across several medical fields. cfDNA is used as a diagnostic biomarker in cancer, prenatal care, and transplantation. In addition, cfDNA may play an unrecognized role in biological processes that are involved in or underlying various disease states, for example, inflammation. Elevated levels of cfDNA are associated with various elements of CVD, cardio-metabolic risk factors, and autoimmune diseases. Mitochondrial cfDNA and neutrophil extracellular traps may play distinct roles. Total circulating cfDNA may reflect the unspecific accumulation of stressors and the organism's susceptibility and resilience to such stressors. As such, cfDNA, in a stressful situation, may provide predictive value for future development of CVD. We suggest exploring such possibility through a large-scale prospective cohort study of pregnant women. Summary There is no doubt that cfDNA is a valuable biomarker. For CVD, its potential is indicated but less explored. New studies may identify cfDNA as a valuable circulating cardiovascular risk marker to help improve risk stratification.

Trafficking and effect of released DNA on cGAS-STING signaling pathway and cardiovascular disease

“…During this process, DNA from different sources will be trafficked into cytosol in different ways, including endocytosis, transmembrane diffusion, phagocytosis, and receptor-mediated endocytosis, thus activating the cGAS-STING signaling pathway ( 5 ). Emerging evidences implicate that cell-free DNA of human circulatory system is significantly correlated with CVD ( 6 , 7 ), and multiple reports have also shown that DNA mediates the activation of cGAS-STING signaling, triggering primary cellular physiologies and tissues pathogenesis, such as CVD ( 8 ). Furthermore, the versatility of cGAS-STING has been uncovered in cellular physiological progress, plays a prominent role in disease pathogenesis.…”