Elsevier

The Lancet

Volume 350, Issue 9082, 27 September 1997, Pages 953-955
The Lancet

Hypothesis
Impaired synthesis of elastin in walls of aorta and large conduit arteries during early development as an initiating event in pathogenesis of systemic hypertension

https://doi.org/10.1016/S0140-6736(96)10508-0Get rights and content

Summary

There is much evidence that people who had low birthweight tend to have higher blood pressure in later life. However, the mechanisms that mediate this relation are unknown. We argue that, in fetuses whose growth is impaired, synthesis of elastin in the walls of the aorta and large arteries may be deficient, and that this deficiency would lead to permanent changes in the mechanical properties of these vessels. Over a lifetime, such changes could predispose an individual to higher blood pressure, increased left-ventricular mass, and cardiovascular disease.

Section snippets

Molecular basis of aortic compliance

The aorta's elastic properties depend largely on the presence of a long-lived scleroprotein—elastin–in the vessel wall. Elastin accounts for 4–50% of the dry weight of the tissue in the thoracic aorta, and is a major component in the abdominal aorta and carotid arteries.4 Aortic elastin is arranged in multiple concentric lamellae, interspersed with smooth muscle and collagen. The number of elastic lamellae is greatest in the proximal part of the aorta. They begin to develop early in fetal life,

Effects of ageing

By middle age, the human aorta has undergone about two billion cycles of expansion and contraction. The effect of cyclic mechanical stress on any material is gradually to reorganise its molecular structure, and to cause its fracture at a load it could previously bear. In the aorta, the fatiguing effects of cyclic stress lead to fracture of elastin fibres and transfer of stress to collagen fibres.12 This process is visible on microscopy as a fragmentation and loss of regularity in the elastic

Regulation of vascular elastogenesis during development

Experiments in animals have shown that synthesis of elastin in the tunica media of developing arteries is influenced by local haemodynamic conditions. For example, at birth, in rabbits, when pulmonary and systemic pressures are similar, the ratios of elastin to collagen in the pulmonary artery and the aorta are the same. 2 months after birth, by which time pulmonary pressure has decreased from 40 mm Hg to 15 mm Hg, and systemic pressure increased to 80 mm Hg, the ratio of elastin to collagen in

Hypothesis

A 1996 systematic review of 34 studies, based on more than 66 000 people, found that in both adults and prepubertal children, there was a consistent negative relation between birthweight and current blood pressure.27 One mechanism that might underlie this association is impairment in elastin synthesis in fetuses of retarded growth during a critical period of blood-vessel development. This impairment may result from haemodynamic changes in the fetal circulation that accompany intrauterine growth

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