HypothesisImpaired synthesis of elastin in walls of aorta and large conduit arteries during early development as an initiating event in pathogenesis of systemic hypertension
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
References (27)
- et al.
Arterial distensibility and left ventricular hypertrophy in patients with sustained essential hypertension
Am Heart J
(1991) Pulse wave velocity as a marker of vascular disease
Lancet
(1996)- et al.
Aorta elastin turnover in normal and hypercholesterolemic Japanese quail
Biochim Biophys Acta
(1980) - et al.
A new in vitro system for studying cell response to mechanical stimulation: different effects of cyclic stretching and agitation on smooth muscle cell biosynthesis
Exp Cell Res
(1977) Structure and function of the arteries in hypertension
Am Heart J
(1987)- et al.
Fetal cardiac function in intrauterine growth retardation
Am J Obstet Gynecol
(1991) - et al.
Risk factors for changes in aorto-iliac arterial compliance in healthy men
Atherosclerosis
(1986) - et al.
Structure and metabolism of arterial elastin
Int Rev Exp Pathol
(1977) Elastic lamina growth in the developing mouse aorta
J Histochem Cytochem
(1995)- et al.
Rapid accumulation of elastin and collagen in the aortas of sheep in the immediate perinatal period
Circ Res
(1992)