The aorta: built to last a lifetime?

Abstract

The pulse pressure generated by the heart is determined by the hydraulic input impedance of the circulation which, in turn is governed by the elastic properties and structural arrangement of elastin, a protein found in the arterial walls of all but the simplest vertebrates. We suggest on the basis of scaling arguments, that pulse pressure depends on the elastic properties of the protein elastin and is independent of body mass. Elastin which, unlike other proteins has a turnover rate close to zero, undergoes fatigue failure in arteries due to cyclic stress, becoming progressively fragmented with age and gradually being replaced by much stiffer fibrous tissue. These changes are well advanced after 1 billion heartbeats, by which time most animals, whatever their size or heart-rate, are nearing the end of their lives. In man this number is achieved by the age of 30 years, which from an evolutionary point of view, is close to the end of useful life. The progressive failure of elastin with age and the consequent increase in arterial stiffness leads to an inexorable rise in blood pressure. Epidemiological investigations have found that raised blood pressure in middle age is associated with impaired fetal growth. Animal experiments have shown that rats whose mothers were deprived of protein while pregnant (to simulate intra-uterine growth retardation) have stiffer aortas which contain less elastin. Thus elastin in the aortas of individuals who are destined to become hypertensive as they age will undergo fatigue failure sooner than their normotensive counterparts. Over a lifetime, such changes will predispose to higher levels of blood pressure, increased left ventricular mass and generalized cardiovascular disease.