Lifelong Cyclic Mechanical Strain Promotes Large Elastic Artery Stiffening: Increased Pulse Pressure and Old Age-Related Organ Failure.

The arterial wall is under a huge mechanical constraint imposed by the cardiac cycle that is bound to generate damage with time. Each heartbeat indeed imposes a pulsatile pressure that generates a vascular stretch. Lifetime accumulation of pulsatile stretches will eventually induce fatigue of the elastic large arterial walls, such as aortic and carotid artery walls, promoting their stiffening that will gradually perturb the normal blood flow and local pressure within the organs, and lead to organ failure. The augmented pulse pressure induced by arterial stiffening favours left ventricular hypertrophy because of the repeated extra work against stiff high-pressure arteries, and tissue damage as a result of excessive pulsatile pressure transmitted into the microcirculation, especially in low resistance/high-flow organs such as the brain and kidneys. Vascular aging is therefore characterized by the stiffening of large elastic arteries leading to a gradual increase in pulse pressure with age. In this review we focus on the effect of age-related stiffening of large elastic arteries. We report the clinical evidence linking arterial stiffness and organ failure and discuss the molecular pathways that are activated by the increase of mechanical stress in the wall. We also discuss the possible interventions that could limit arterial stiffening with age, such as regular aerobic exercise training, and some pharmacological approaches.