Grant: Travel Awards - Institute Community Support

Aortic valve stenosis (AVS) is the most common cause of surgical valve replacement worldwide. Previous studies have shown that the urotensin II (UII), a protein that affects blood vessel diameter, is upregulated in atherosclerosis and several other cardiovascular diseases, however its role in the development of AVS remains to be determined. Here, we investigated the role of UII, urotensin-related peptide (URP) and the urotensin receptor (UT) in AVS. We first examined the plasma level of UII in patients with AVS. Circulating UII levels in AVS patients were significantly elevated compared to healthy controls, which was associated with older age, high body mass index, elevated levels of bad cholesterol and high blood pressure. We also found a trend towards significance in stenotic females having elevated plasma level of UII age-matched males. Using diseases aortic valve, we found expression of UII, URP and UT at both the protein and messenger RNA level. Expression of these proteins were significantly associated with calcification, inflammation and fat deposition. To further understand the role of the urotensin system in the development of AVS, we isolated the main source of cells from healthy aortic valves, the human aortic valve interstitial cells (HAVICs) and treated them with UII and URP proteins. HAVICs treated with UII and URP increased calcium deposition, while reducing the ability of the cells to excrete cholesterol. Only UII treatment, however, decreased expression of the cholesterol transporter, ABCA1. Together, these data suggest that the urotensin system plays a role in the development of AVS and warrants further investigation. Better understanding of this system will aid in the development of novel therapeutics to prevent and treat patients with AVS.