Cardiovascular Effects of Exercise Training: Molecular Mechanisms

In the natural habitat of our ancestors, physical activity was not a preventive intervention but a matter of survival. In this hostile environment with scarce food and ubiquitous dangers, human genes were selected to optimize aerobic metabolic pathways and conserve energy for potential future famines.1 Cardiac and vascular functions were continuously challenged by intermittent bouts of high-intensity physical activity and adapted to meet the metabolic demands of the working skeletal muscle under these conditions. When speaking about molecular cardiovascular effects of exercise, we should keep in mind that most of the changes from baseline are probably a return to normal values. The statistical average of physical activity in Western societies is so much below the levels normal for our genetic background that sedentary lifestyle in combination with excess food intake has surpassed smoking as the No. 1 preventable cause of death in the United States.2 Physical activity has been shown to have beneficial effects on glucose metabolism, skeletal muscle function, ventilator muscle strength, bone stability, locomotor coordination, psychological well-being, and other organ functions. However, in the context of this review, we will focus entirely on important molecular effects on the cardiovascular system. The aim of this review is to provide a bird's-eye view on what is known and unknown about the physiological and biochemical mechanisms involved in mediating exercise-induced cardiovascular effects. The resulting map is surprisingly detailed in some areas (ie, endothelial function), whereas other areas, such as direct cardiac training effects in heart failure, are still incompletely understood. For practical purposes, we have decided to use primarily an anatomic approach to present key data on exercise effects on cardiac and vascular function. For the cardiac effects, the left ventricle and the cardiac valves will be described separately; for the vascular effects, we will follow the arterial vascular …