0416 : Vascular smooth muscle cells are responsible for a prothrombotic phenotype of spontaneously hypertensive rat arteries

Abstract

The hypothesis that hypertension confers a hypercoagulable state arises from the complications associated with hypertension, stroke and myocardial infarction. Our objective was to determine whether spontaneous hypertension causes changes in the thrombin generating capacity of the vascular wall. We used spontaneously hypertensive rats (SHR) compared with Wistar rats. The addition of thoracic aorta rings of SHR to a Wistar or SHR plasma pool resulted in a greater increase in thrombin generation compared to the addition of equivalent rings from Wistar. Comparison of 5 week-old and 12 week-old rats indicate that established hypertension is required to induce increased thrombin generation within the vessel wall. Whereas no difference was observed for endothelial cells, thrombin formation was higher at the surface of cultured aortic smooth muscle cells (SMCs) from SHR than from Wistar. Exposure of negatively-charged phospholipids was higher on SHR than on Wistar aortic rings as well as on SMCs. Tissue factor activity was higher in SHR SMCs. Twelve week-old SHR exhibited accelerated FeCl3-induced thrombus formation in carotid arteries and the resulting occlusive thrombi are disaggregated by blockade of glycoprotein Ibα-von Willebrand factor interactions. SHR SMCs were more sensitive to thrombininduced proliferation than Wistar SMCs. This cellular effect was totally abolished by a protease-activated receptor 1 inhibitor. The prothrombotic phenotype of the SHR vessel wall was due to the ability of SMCs to support greater thrombin generation and resulted in accelerated occlusive thrombus formation after arterial injury, which is sensitive to glycoprotein Ibα-von Willebrand factor inhibitors.