The CGAS-STING1 Pathway as a Mediator of Innate Immune Response in Cardiovascular Disease

Abstract

The innate immune response, a rapid and cell-autonomous response of the cell to the pathogens, recognizes the external as well as the internal pathogens, such as self-DNA, released from the damaged cells. The response activates a set of molecules that induce the expression of proinflammatory cytokines and chemokines and leads to inflammation, fibrosis, and cell death. The innate immune response comprised of DNA-sensing protein cyclic guanosine monophosphate–adenosine monophosphate synthase (CGAS) and its downstream molecules, the stimulator of interferon genes 1 (STING1), TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and nuclear factor kappa B (NFκB), are activated in several cardiovascular diseases, including hereditary cardiomyopathies, myocardial infarction, hypertension, atherosclerosis, and aortic aneurysm. The genetic deletion of key molecules in this pathway, such as CGAS, STING1, and interferon regulatory factor 3, affords salubrious effects, including improving survival and cardiac dysfunction, rendering the CGAS-STING1 pathway an attractive therapeutic target in cardiovascular disease.