Merck Canadian Cardiovascular Society (CCS) ePosters ADVANCES IN VASCULAR BIOLOGY Monday, October 23, 2017 297 POST-STENOTIC DILATATION IN A MURINE MODEL OF AORTIC STENOSIS AND ITS APPLICABILITY TO BICUSPID AORTOPATHY M Lee Toronto, Ontario BACKGROUND: Bicuspid aortic valve (BAV) is the most common congenital cardiac defect with an incidence of 1 to 2%. Aortic dilation occurs in 50% of BAVs and may progress to dissection or rupture. Aberrant shear stress is one of the principle etiologies of BAV aortopathy. However, an experimental model of ascending aortic dilation from stenotic blood flow has not yet been established. We developed a murine model of aortic stenosis with aortic dilation to investigate the molecular effects of isolated increases in shear stress during the early phase of ascending aortic remodeling and assess their applicability to BAV aortopathy. METHODS: C57BL/6 mice underwent supravalvular constriction of the ascending aorta. Maximum flow velocity, pressure gradient, ascending aortic diameter, and left ventricular function and dimension were measured using weekly echocardiography. Ascending aortas were collected at 3 days, 2 weeks, and 4 weeks after constriction for analysis of tissue inhibitors of matrix metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs) transcription. Ascending aortic segments correspond- ing to the region of increased shear stress by color flow Doppler were collected at 4 weeks after constriction for histology. RESULTS: Constriction was applied at 2.69  0.06 mm above the aortic valve (n¼27; standard error of the mean). Maximum flow velocity and pressure gradient increased after constriction and remained elevated from baseline (n¼27; p0.0001). Progressive ascending aortic dilation occurred weekly following constriction (n¼7; p¼0.0003). Ascending aortas showed 28.5  2.1% dilation by Week 4 (n¼27; p0.0001). Elastin disruption was localized to the greater curvature corresponding to the region of increased shear stress by color flow Doppler while the lesser curvature remained unchanged. MMP2 and MMP9 showed increased transcription at Week 2 (n¼4; p0.05). TIMP1 and TIMP2 showed a trend towards reduced transcription at Day 3 (n¼4; p>0.05). CONCLUSION: Our preliminary results in a novel murine model of aortic stenosis and post-stenotic dilation suggest that higher mechanical stress initiates aortic dilation through increased transcription of MMP2 and MMP9 with localized elastin disruption. MMP inhibition may be a potential ther- apeutic target in the early phase of post-stenotic aortic remodeling that may include BAV disease. Application of our technique using genetic murine models of BAV may help to establish future experimental therapy to address the hemo- dynamic component of BAV aortopathy. CSE Travel Bursary Research Award Winner 298 CAROTID PLAQUE NEOVASCULARIZATION IS ASSOCIATED WITH SIGNIFICANT CORONARY ARTERY DISEASE AND ACUTE MYOCARDIAL INFARCTION L Mantella, K Colledanchise, T Zhu, M Bullen, M Hétu, J Abunassar, A Johri Kingston, Ontario BACKGROUND: It is thought that the majority of cardiovascular (CV) events are caused by vulnerable plaque. Such lesions are rupture-prone, in part due to neovascularization. It is postu- lated that plaque vulnerability may be a systemic process and that vulnerable lesions may co-exist at multiple sites in the vascular bed. We sought to examine whether carotid plaque vulnerability, characterized by intraplaque neovascularization detected by contrast-enhanced ultrasound (CEUS), is associ- ated with significant coronary artery disease (CAD) and acute myocardial infarction (MI). Abstracts S183