Mitochondrial Dysfunction and Inflammaging in Heart Failure: Novel Roles of CYP-Derived Epoxylipids

Abstract

Age-associated changes leading to a decline in cardiac structure and function contribute to the increased susceptibility and incidence of cardiovascular diseases (CVD) in elderly individuals. Indeed, age is considered a risk factor for heart failure and serves as an important predictor for poor prognosis in elderly individuals. Effects stemming from chronic, low-grade inflammation, inflammaging, are considered important determinants in cardiac health; however, our understanding of the mechanisms involved remains unresolved. A steady decline in mitochondrial function is recognized as an important biological consequence found in the aging heart which contributes to the development of heart failure. Dysfunctional mitochondria contribute to increased cellular stress and an innate immune response by activating the NLRP-3 inflammasomes, which have a role in inflammaging and age-related CVD pathogenesis. Emerging evidence suggests a protective role for CYP450 epoxygenase metabolites of N-3 and N-6 polyunsaturated fatty acids (PUFA), epoxylipids, which modulate various aspects of the immune system and protect mitochondria. In this article, we provide insight into the potential roles N-3 and N-6 PUFA have modulating mitochondria, inflammaging and heart failure.