Extracellular nucleic acids in immunity and cardiovascular responses: between alert and disease

Severe inflammatory complications are a potential consequence in patients with predetermined conditions of infections, pulmonary diseases, or cardiovascular disorders. Notably, the amplitude of the inflammatory response towards these complications can dictate the disease progression and outcome. During the recent years, evidence from basic research as well as from clinical studies has identified self-extra cellular nucleic acids as important players in the crosstalk between immunity and cardiovascular diseases. These stress- or injury-induced endogenous polymeric macromolecules not only serve as alarmins or Danger-associated molecular patterns (DAMPs), but their functional repertoire goes far beyond such activities in innate immunity. In fact, (patho-) physiological functions of self-extracellular DNA and RNA are associated and in many cases causally related to arterial and venous thrombosis, atherosclerosis, ischemia-reperfusion injury or tumour progression. Yet, the underlying molecular mechanisms are far from being completely understood. Interestingly enough, however, novel antagonistic approaches in vitro and in vivo, particularly using natural endonucleases or synthetic nucleic acid binding polymers, appear to be promising and safe therapeutic options for future studies. The aim of this review article is to provide an overview of the current state of (patho-) physiological functions of self-extracellular nucleic acids with special emphasis on their role as beneficial / alerting or adverse / damaging factors in connection with immune responses, inflammation, thrombosis, and cardiovascular diseases.