Context

Increased arterial stiffness is an important consequence of the natural ageing process, and it represents a major risk factor for cardiovascular diseases. Approximately 4 million people in Europe die of cardiovascular disease each year. Among arterial diseases, hypertension is estimated to affect 1.56 billion people in the world by 2025. Altogether, it is increasingly evident that there is significant clinical value in assessing and developing medical strategies to counteract the phenomenon of increased vascular stiffness. This represents a wide pharmacological market at the national, European and worldwide levels.

The passive stiffness of elastic arteries is mainly determined by two major extracellular matrix proteins of the arterial wall, i.e. elastin and collagen.

Elastin-rich elastic fibres allow the large artery walls to transform the pulsatile blood flow ejected by the heart into a continuous blood flow in the peripheral arteries (Windkessel effect). Dysfunctions are highly correlated with diseases such as artery stenosis, aneurysm, hypertension or cardiac hypertrophy, which have strong repercussions on arterial biomechanics and can threaten the vessel integrity. Loss of elasticity and induced consequences on the vascular function are observed in normal ageing, and in syndromic elastogenesis-related genetic diseases which include Williams-Beuren syndrome (WBS, OMIM #194050), supra-valvular aortic stenosis (SVAS, OMIM #185500) and autosomal dominant cutis laxa (ADCL, OMIM #123700). Recent studies have also shown it can be associated with pathological conditions such as the sleep apnea syndrome.

Setting aside surgery (angioplasty, stenting and coronary bypass for instance) which does not address the root causes and for which the benefit-risk ratio has to be carefully evaluated, there is currently no treatment for preventing, blocking or treating any loss of elasticity. Classical pharmacotherapy aiming at elastin restoration could prevent and cure arterial malformations and subsequent cardiovascular dysfunctions in conditions involving arterial wall remodelling. However, side effects such as hypertrichosis or oedema make this strategy rather complex to use.

It therefore appears, from a biomechanical point of view, that the introduction of an entity that provides elasticity within the arterial wall would be the most trivial action to stop arterial stiffening, but remains currently limited due to chemo-biological issues.