Interferon regulatory factor signalings in cardiometabolic diseases.

Abstract

Cardiometabolic diseases comprise a spectrum of interconnected pathological alterations in metabolic organs and in the cardiovascular system that occur alone or simultaneously.1 Although great efforts have been undertaken to develop therapeutic agents (eg, statins and tissue-type plasminogen activator) for these unfavorable conditions, epidemiological data demonstrate that the prevalence of cardiometabolic diseases is continuously increasing and constitutes the heaviest burden on global health and economic development.2 An ambiguous understanding of the latent pathogenesis of cardiometabolic diseases might be responsible for their consistently high morbidity and mortality. In recent years, the discovery of a close interaction between the inflammatory response and the various cardiometabolic disorders has provided novel insight into the cause of these pathological conditions. Chronic low-grade inflammation has been identified as an important mediator of various cardiometabolic dysfunctions and has been shown to be involved in the entire process of lipid profile disturbance and the resultant hepatic steatosis, obesity, and hyperlipidemia, leading to severe cardiovascular disease.3–5 However, the inhibition of inflammation unfortunately failed to block the long-term development of cardiometabolic diseases and rendered the host susceptible to infection,6 suggesting that inflammation might only represent an outcome or a regulator of these diseases rather than the principal pathogenic factor. Therefore, what is the actual cause of cardiometabolic diseases? Innate immunity, an evolutionarily ancient and universal response of the host to defend against infection and injury, underlies inflammatory responses that is triggered by innate immune molecular cascades.7 Most recently, these immune signaling cascades have been not only found to extend beyond the purview of the immune system but also involved in or even play a central mechanistic role in broader physiological functions, including the function in the cardiometabolic system. A clear understanding of the mechanistic basis for the link between innate immunity and cardiometabolic diseases …