Do Changes in Innate Immunity Underlie the Cardiovascular Benefits of Exercise?

Abstract

It is well established that exercise promotes health and reduces the development and progression of cardiovascular disease (CVD) (1). Traditional risk factors for CVD, such as dyslipidemia, hypertension, and diabetes mellitus, as well as all-cause mortality, are inversely correlated with cardiorespiratory fitness (2). With advancing technology and decreasing global trends in physical activity, physical inactivity is now the fourth leading cause of death worldwide (3). Furthermore, 3 million deaths per year and an estimated $53.8 billion in economic costs are lost due to insufficient physical activity (4). Although exercise promotes numerous salutary effects on the cardiovascular system, several human studies have concluded that, after controlling for reductions in traditional CVD risk factors, the beneficial effects of regular exercise are attributable to a decrease in chronic inflammation and inflammatory mediator production (1, 5–8). These clinical findings are complemented by animal studies that report regular moderate intensity exercise decreases the risk for chronic disease development through modification of the immune system (9, 10). Despite the immunoregulatory effects of exercise, the underlying cellular mechanisms and signaling pathways that promote cardiovascular health remain unknown. Identifying key determinants by which exercise modulates inflammatory responses likely offer new therapeutic targets for the treatment of cardiovascular disease. Given that the innate immune system is responsible for initiating most inflammatory responses and causally contributes to cardiac pathology and repair, we have focused this opinion manuscript on the potential role of neutrophils and macrophages in mediating the cardioprotective effects afforded by exercise.