Exercise regulates cardiac metabolism: Sex does matter

Cardiac substrate utilization remains a critical focus for the research community.1 Research has acknowledged the role of metabolic flexibility in the development and progression of cardiac dysfunction during a variety of diseases and conditions.2,3 Under resting basal conditions,the heart relies on fatty acid metabolism as the primary energy source with glucose,lactate,ketone bodies,pyruvate,acetate,and branched-chain amino acids contributing as substrates depending on substrate availability,hormonal status,and myocardial conditioning.4 In addition to pathological states,physiological states,such as acute exercise,induce dynamic changes in substrate metabolism,including nearly a 10-fold increase in myocardial oxygen consumption.3,5 To meet the increased demand for energy during and after a bout of exercise,the heart muscle must exhibit metabolic flexibility and selectively utilize different substrates for adenosine triphosphate production.Moreover,metabolic substrate adaptations depend on the frequency,intensity,duration,and mode of exercise while multiple metabolic fluxes,such as the use,storage and mobilization of substrates must be coordinated to maintain energy homeostasis.1,2 Although many different processes of exercise-induced regulation and metabolic remodeling have been identified,35 the effect of exercise on cellular metabolism and the landscape of metabolic pathway regulation in response to both acute exercise and chronic exercise training remain unclear.

Circular RNAs in Cardiovascular Diseases:Regulation and Therapeutic Applications

Cardiovascular disease is one of the leading causes of mortality worldwide.Recent studies have shown that circular RNAs(circRNAs)have emerged as important players in the prevention and treatment of cardiovascular diseases.circRNAs are a class of endogenous noncoding RNAs that are generated by back-splicing and are involved in many pathophysiological processes.In this review,we outline the current research progress on the regulatory roles of circRNAs in cardiovascular diseases.Further,new technologies and methods available for identifying,validating,synthesizing,and analyzing circRNAs,as well as their applications in therapeutics,are highlighted here.Moreover,we summarize the increasing insights into the potential use of circRNAs as circulating diagnostic and prognostic biomarkers.Finally,we discuss the prospects and challenges of circRNA therapeutic applications for cardiovascular disease therapy,with a particular focus on developing circRNA synthesis and engineering delivery systems.

Exercise training maintains cardiovascular health:signaling pathways involved and potential therapeutics

Exercise training has been widely recognized as a healthy lifestyle as well as an effective non-drug therapeutic strategy for cardiovascular diseases(CVD).Functional and mechanistic studies that employ animal exercise models as well as observational and interventional cohort studies with human participants,have contributed considerably in delineating the essential signaling pathways by which exercise promotes cardiovascular fitness and health.First,this review summarizes the beneficial impact of exercise on multiple aspects of cardiovascular health.We then discuss in detail the signaling pathways mediating exercise’s benefits for cardiovascular health.The exercise-regulated signaling cascades have been shown to confer myocardial protection and drive systemic adaptations.The signaling molecules that are necessary for exercise-induced physiological cardiac hypertrophy have the potential to attenuate myocardial injury and reverse cardiac remodeling.Exercise-regulated noncoding RNAs and their associated signaling pathways are also discussed in detail for their roles and mechanisms in exercise-induced cardioprotective effects.Moreover,we address the exercise-mediated signaling pathways and molecules that can serve as potential therapeutic targets ranging from pharmacological approaches to gene therapies in CVD.We also discuss multiple factors that influence exercise’s effect and highlight the importance and need for further investigations regarding the exercise-regulated molecules as therapeutic targets and biomarkers for CVD as well as the cross talk between the heart and other tissues or organs during exercise.We conclude that a deep understanding of the signaling pathways involved in exercise’s benefits for cardiovascular health will undoubtedly contribute to the identification and development of novel therapeutic targets and strategies for CVD.