oa Pentraxin 3 is a Potential Diagnostic Marker for Aortic Stenosis

Pentraxin 3 (ptx3) is a member of the long pentraxin family and is rapidly produced and released by many cell types, including endothelial cells, in response to primary inflammatory signals. In our preliminary work, PTX3 gene expression was significantly increased in aortic valve tissue following exposure to elevated cyclic pressure. Consequently, we hypothesized that ptx3 would be a useful biomarker for the early diagnosis of aortic valve sclerosis. Isolated aortic VICs were treated with Angiotensin II (300nM), TNF-alpha (10 ng/ml) or elevated cyclic pressure for six hours. The cell culture supernatant was collected and used to determine ptx3 protein expression using ELISA. Total RNA was isolated from the cells and PTX3 gene expression was determined using semi-quantitative RT-PCR. In addition to cell culture studies, ptx3 protein expression was determined in hypertensive New Zealand White rabbits. Rabbits underwent Goldblatt one-clip/one-kidney surgery to induce hypertension (n=5). Four sham models served as a control. Blood pressure, echocardiography data and serum samples were collected at 0, 2 and 4 months. After 4 months, rabbits were euthanized and aortic valve tissue was collected for histological and gene expression analysis. Data from the cell culture studies showed that elevated cyclic pressure caused an increase in PTX3 gene expression and ptx3 protein expression. However, no significant changes were observed in gene or protein expression from cells treated with Ang II or TNF-alpha. Data collected from the animal model showed that blood pressure increased significantly for the experimental group but not the control group. Levels of ptx3 protein were measured from the serum and showed a slight increase over the four-month course of the experiments. The data suggest that ptx3 expression is mechanosensitive in the aortic valve and is not stimulated by biochemical factors such as TNF-alpha or Ang II. The increase in ptx3 expression in hypertensive rabbits demonstrates that this could be a potential diagnostic marker for aortic stenosis.