Cardiovascular Research Advance Access [Accepted Manuscript] published online on July 7, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp236
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vascular endothelial aging, heartbeat after heartbeat
Université de Montréal, Faculty of Medicine, Department of Surgery, Montreal Heart Institute, Montréal, Canada
Author for correspondence: Eric Thorin, Montreal Heart Institute, Research Centre, 5000, rue Bélanger, Montréal (Québec) H1T 1C8, Canada. Phone: 1 514 376 3330 Fax: 1 514 376 1355 Email: eric.thorin{at}umontreal.ca
The vascular endothelium starts to age at the first heartbeat. There is no longer a need to demonstrate that an increased resting heart rate—above 70 beats per minute—is associated with the onset of cardiovascular events and reduces lifespan in humans. Each cardiac cycle imposes a mechanical constraint on the arteries, and we would like to propose that this mechanical stress damages the vascular endothelium, its dysfunction being the prerequisite for atherogenesis. Consequently, reducing heart rate could protect the endothelium and slow the onset of atherosclerosis. The potential mechanisms by which reducing heart rate could be beneficial to the endothelium are likely a combination of a reduction in mechanical stress and tissue fatigue and a prolongation of the period of steady laminar flow, and thus sustained shear stress, between each systole. With age, irreparable damage accumulates in endothelial cells and leads to senescence, which is characterized by a pro-atherogenic phenotype. In the body, the highest mechanical stress occurs in the coronary vessels, where blood only flows during diastole and even reverses during systole; thus, coronary arteries are the prime site of atherosclerosis. All classical risk factors for cardiovascular diseases add up, to accelerate atherogenesis, but hypertension, which further raises mechanical stress, is likely the most damaging. By inducing flow through the arteries, the heart rate determines shear stress and its stability: mechanical stress and the associated damage induced by each systole are efficiently counteracted by the repair capacities of a healthy endothelium. The maintenance of a physiological, low heart rate may be key to prolonging the endothelial healthy lifespan and thus, vascular health.
KEYWORDS endothelium; resting heart rate; mechanical stress; cellular maintenance; cellular repair; atherosclerosis
Time for primary review: 18 Days