Caffeic acid ethanolamide prevents cardiac dysfunction through sirtuin dependent cardiac bioenergetics preservation

Abstract

BackgroundCardiac oxidative stress, bioenergetics and catecholamine play major roles in heart failure progression. However, the relationships between these three dominant heart failure factors are not fully elucidated. Caffeic acid ethanolamide (CAEA), a synthesized derivative from caffeic acid that exerted antioxidative properties, was thus applied in this study to explore its effects on the pathogenesis of heart failure.ResultsIn vitro studies in HL-1 cells exposed to isoproterenol showed an increase in cellular and mitochondria oxidative stress. Two-week isoproterenol injections into mice resulted in ventricular hypertrophy, myocardial fibrosis, elevated lipid peroxidation, cardiac adenosine triphosphate and left ventricular ejection fraction decline, suggesting oxidative stress and bioenergetics changes in catecholamine-induced heart failure. CAEA restored oxygen consumption rates and adenosine triphosphate contents. In addition, CAEA alleviated isoproterenol-induced cardiac remodeling, cardiac oxidative stress, cardiac bioenergetics and function insufficiency in mice. CAEA treatment recovered sirtuin 1 and sirtuin 3 activity, and attenuated the changes of proteins, including manganese superoxide dismutase and hypoxia-inducible factor 1-α, which are the most likely mechanisms responsible for the alleviation of isoproterenol-caused cardiac injuryConclusionCAEA prevents catecholamine-induced cardiac damage and is therefore a possible new therapeutic approach for preventing heart failure progression.

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential

“…CAPE has been reported to extend the lifespan of a mouse model of amyotrophic lateral sclerosis (ALS) (Fontanilla et al, 2012). Additionally, an ethanolamide derivative (CAEA) has been shown to activate AMPK as well as SIRTs and ameliorate cardiac damage in a mouse model (Lee et al, 2015b).…”

Pure Polyphenols Applications for Cardiac Health and Disease

“…Moreover, caffeic acid and chlorogenic acid, compounds present in berries extract, are able to limit oxidative stress induced by hydrogen peroxide in chick embryo ventricular myocytes [173]. Furthermore, isoproterenolinduced oxidative stress in HL-1 mouse atrial muscle cell line was reverted by treatment with caffeic acid [174]. In RNVC, chlorogenic acid inhibits isoproterenol-induced cardiac hypertrophy by attenuating NF-κB signaling pathway and suppressing ROS [175].…”

Regulation of Sirtuin‐Mediated Protein Deacetylation by Cardioprotective Phytochemicals

“…They include quercetin, epigallocatechin-3-gallate, bakuchiol, tyrosol, and berberine [ 81 – 86 ]. Nutraceuticals that function as activators of Sirt1 include docosahexaenoic acid, alpha-lipoic acid, sulforaphane, and caffeic acid ethanolamide, although the mechanisms by which they activate sirtuins remain to be elucidated [ 26 , 89 – 97 ]. Most of these functional molecules share common molecular targets and exert their actions, for example, by stimulation of AMPK- α , eNOS, PGC1- α , and superoxide dismutase or inhibition of NF- κ B and proapoptotic molecules (e.g., Bax and caspase 3).…”