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Conduit arteries become stiffer with age due to alterations in their morphology and the composition of the their major structural proteins, elastin and collagen. The elastic lamellae undergo fragmentation and thinning, leading to ectasia and a gradual transfer of mechanical load to collagen, which is 100-1000 times stiffer than elastin. Possible causes of this fragmentation are mechanical (fatigue failure) or enzymatic (driven by matrix metallo proteinases (MMP) activity), both of which may have genetic or environmental origins (fetal programming). Furthermore, the remaining elastin itself becomes stiffer, owing to calcification and the formation of cross-links due to advanced glycation end-products (AGEs), a process that affects collagen even more strongly. These changes are accelerated in the presence of disease such as hypertension, diabetes and uraemia and may be exacerbated locally by atherosclerosis. Raised MMP activity, calcification and impaired endothelial function are also associated with a high level of plasma homocysteine, which itself increases with age. Impaired endothelial function leads to increased resting vascular smooth muscle tone and further increases in vascular stiffness and mean and/or pulse pressure. The effect of increased stiffness, whatever its underlying causes, is to reduce the reservoir/buffering function of the conduit arteries near the heart and to increase pulse wave velocity, both of which increase systolic and pulse pressure. These determine the peak load on the heart and the vascular system as a whole, the breakdown of which, like that of any machine, depends more on the maximum loads they must bear than on their average. Reversing or stabilising the increased arterial stiffness associated with age and disease by targeting any or all of its causes provides a number of promising new approaches to the treatment of systolic hypertension and its sequelae, the main causes of mortality and morbidity in the developed world. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In the last 40 years, as techniques and materials have improved, the success rate of vascular prostheses with a diameter greater than 6mm has risen steadily, 5-year survival rates exceeding 95% in most centres. With smaller grafts no comparable improvement has occurred, the majority failing within 5 years, usually as a result of intimal hyperplasia and, ultimately atherosclerosis, in and around the downstream anastomosis. Clinical evidence suggests that the patency rates of small grafts are improved by matching the elastic properties of the graft to that of the artery into which it is placed. Although there is little reliable evidence that 'elastic mismatch' per se is the cause of intimal hyperplasia, it is generally accepted that mechanical factors are important in its genesis. These include disturbed flow at the anastomosis leading to fluctuations in shear stress at the endothelium (a known cause of intimal hyperplasia in normal arteries), injury due to suturing and stress concentration at the anastomosis. Few suitable materials or techniques have yet been developed to improve the long-term survival rates of small grafts. Recent advances in tissue engineering in which prostheses are manufactured by culturing vascular smooth muscle cells on a tubular scaffold of biodegradable polymer may ultimately make it possible to manufacture biologically and haemodynamically compatible grafts with diameters as small as 1mm., (Copyright 2000 John Wiley & Sons, Ltd.)

It is known that the distribution of stress and strain in the vessel wall is not uniform. We believe that this explains the location of the plane of dissection in dissecting aneurysms of large elastic arteries. We have investigated the effects of non-uniformity of stress and strain on the thickness of each elastic lamella and on the distribution of intercellular junctions in the media of developing and adult rats, to seek evidence to support this hypothesis. Intercellular junctions were identified by transmission electron microscopy of whole wall sections. A morphometric study of elastic tissue distribution was made on an image analysis computer. Differences were analysed using one-way analysis of variance. There are between six and eight elastic lamellae in the aorta of rats. In the fetus, only the internal elastic lamella is complete; the others were not fully formed by term. In the adult, the inner five elastic lamellae were thicker than the remaining two or three, and smooth muscle cells in the thicker lamellar units had more cell-cell contacts of all types examined. These data support the concept of a difference in stress-resisting properties of the aortic wall on the junctions between the inner two-thirds and the outer third of the media. The findings indicate that, as proposed in theoretical models the innermost lamellae support the high tension. In the adult aorta, the structure is modified to enhance the capacity to resist stress in the internal two-thirds of the media.(ABSTRACT TRUNCATED AT 250 WORDS)