Vascular endothelial ageing, heartbeat after heartbeat

Cardiovasc Res. 2009 Oct 1;84(1):24-32. doi: 10.1093/cvr/cvp236. Epub 2009 Jul 7.

Abstract

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 b.p.m.--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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Aging / physiology*
  • Animals
  • Atherosclerosis / physiopathology
  • Atherosclerosis / prevention & control
  • Baroreflex
  • Benzazepines / therapeutic use
  • Cardiovascular Diseases / etiology
  • Endothelium, Vascular / physiology*
  • Heart Rate*
  • Humans
  • Ivabradine
  • Nitric Oxide / physiology
  • Pulsatile Flow
  • Risk Factors
  • Shear Strength
  • Stress, Mechanical

Substances

  • Adrenergic beta-Antagonists
  • Benzazepines
  • Nitric Oxide
  • Ivabradine

Grants and funding