Ageing of the conduit arteries

Abstract

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.

Tissue elasticity and the ageing elastic fibre

“…Age-related alterations in the mechanical properties of the vascular system have profound effects on human morbidity and mortality (for recent reviews see Greenwald 2007;Mitchell 2008;O'Rourke and Hashimoto 2007). Arteries and veins are composed of three distinct layers, the tunica intima, tunica media, and tunica adventia (Quaglino and PasqualiRonchetti 2002).…”

“…The number of elastic lamellae decreases from 40-70 in conducting arteries such as the aorta, to fewer than ten in the smaller resistance arteries. The compliance and elasticity of the major arteries plays a key role in cardiac function; driving systemic blood flow via the storage of elastic tensile energy in the aorta (Greenwald 2007) and converting pulsatile to steady blood flow (O'Rourke and Hashimoto 2007). Age-related reductions in arterial compliance (known as arteriosclerosis) lead to increases in systolic blood pressure in the aorta, a major risk factor for the development of heart failure (Mitchell 2008;O'Rourke and Hashimoto 2007).…”

Creating a model of diseased artery damage and failure from healthy porcine aorta

“…Disease and ageing, however, alter the respective compositions, leading to often undesirable changes in function. Ageing has been shown to cause a loss of medial elastin followed by an increase in the stiffer collagen fibres, further stiffened by additional cross-linking, to compensate [8,9,10,11]. This results in the elastin-collagen interaction altering and the stiffer collagen fibres being recruited at smaller deformations, leading to an observed stiffening of the arterial wall.…”

Differential effects of relaxin deficiency on vascular aging in arteries of male mice

“…A major risk factor for cardiovascular disease is increased vascular stiffness, which is also associated with aging (Greenwald 2007;Zieman et al 2005). Remodeling of the vessel wall components (vascular smooth muscle cells (VSMCs) and extracellular matrix) contributes to the modulation of passive mechanical wall properties of blood vessels and influence vascular stiffness and compliance (Zieman et al 2005).…”

“…The vascular remodeling that occurs with aging has commonly been associated with increased vascular stiffness (Cecelja and Chowienczyk 2012). Outward hypertrophic remodeling (increased luminal diameter and wall thickness) is also an established characteristic of aged arteries (Greenwald 2007;Sawabe 2010). The effects of aging on the vasculature largely arise from research on larger conduit arteries.…”