Stiffness of the aorta, measured as pulse wave velocity (PWV), is a major cause of increased pulse pressure leading to isolated systolic hypertension in the elderly. It is now accepted as significant predictor of cardiovascular risk. However, progression of arterial stiffness can vary markedly in different populations.
While arterial stiffness is well understood in relation to arterial mechanics, the fundamental cellular and molecular mechanisms underlying the structural modifications of the arterial wall leading to altered mechanical stiffness are gradually being established. These include cell signaling pathways affecting protein modification leading to alteration of the extracellular matrix (ECM) of the artery wall. Two mechanisms will be presented: (i) arterial calcification mediated by the vascular smooth muscle cells (VSMC); (ii) ECM modification due to cross-linking of matrix components mediated by nitric oxide (NO) pathways in the endothelial cell.
The elucidation of the interaction of cellular and ECM processes affecting arterial stiffness is an important advance in the search for possible therapies to counteract the detrimental effects of increased pulse pressure due to stiffness of large arteries. Once the pathways are identified, target molecules can be interrogated pharmacologically to arrest mineral deposits or reduce crosslinking of ECM components. |
