Extrinsic and Intrinsic Modulators of Inflammation-resolution Signaling in Heart Failure

Chronic and uncleared inflammation is the root cause of various cardiovascular diseases. Fundamentally, acute inflammation is supportive when overlapping with safe clearance of inflammation termed resolution; however, if the lifestyle-directed extrinsic factors such as diet, sleep, exercise, or physical activity are misaligned, that results in unresolved inflammation. Although genetics play a critical role in cardiovascular health, four extrinsic risk factors-unhealthy processed diet, sleep disruption or fragmentation, sedentary lifestyle, thereby, subsequent stress-have been identified as heterogeneous and polygenic triggers of heart failure (HF), which can result in several complications with indications of chronic inflammation. Extrinsic risk factors directly impact endogenous intrinsic factors, such as using fatty acids by immune-responsive enzymes [lipoxygenases (LOXs)/cyclooxygenases (COXs)/cytochromes-P450 (CYP450)] to form resolution mediators that activate specific resolution receptors. Thus, the balance of extrinsic factors such as diet, sleep, and physical activity feed-forward the coordination of intrinsic factors such as fatty acids-enzymes-bioactive lipid receptors that modulates the immune defense, metabolic health, inflammation-resolution signaling, and cardiac health. Future research on lifestyle- and aging-associated molecular patterns is warranted in the context of intrinsic and extrinsic factors, immune fitness, inflammation-resolution signaling, and cardiac health.