Title: Arterial Stiffness As A Therapeutic Target For Isolated Systolic Hypertension: Focus on Vascular Calcification and Fibrosis
Volume: 6
Issue: 1
Author(s): Celine Bouvet, Rachida Essalihi, Liz-Ann Gilbert, Simon Moreau and Pierre Moreau
Affiliation:
Keywords:
Arterial stiffness, elastocalcinosis, vascular fibrosis, matrix metalloproteinases, transforming growth factor, endothelin, nitric oxide
Abstract: Isolated systolic hypertension is the most common form of essential hypertension in patients over 65 years old and is not well controlled by current antihypertensive therapies. Current antihypertensive pharmacology is focused on reducing peripheral resistance and ventricular ejection. However, the increase of systolic blood pressure is mainly a consequence of large artery stiffening. This pathological process seems to be the result of medial arterial calcification (or elastocalcinosis), elastin degradation, extracellular matrix fibrosis and endothelial dysfunction. As a unifying hypothesis, we propose that initial extracellular calcification could promote extracellular matrix-cellular interactions by involving metalloproteinase matrix degradation, leading to the liberation of embedded transforming growth factor-β. This growth factor could promote a cascade of events involving vascular smooth muscle cells that adopt an osteogenic phenotype and express a different set of proteins, such as endothelin, that appear to play a central role in medial calcification and fibrosis. This review highlights the evidence supporting the hypothesis. It also presents the effects of current drugs on calcification and/or fibrosis in experimental model of isolated systolic hypertension to illustrate where we stand in our efforts to modify the process of arterial stiffening.
