Abstract 041: Distinct populations of cell derived microvesicles in Angiotensin II-induced hypertension

Abstract

Background: Hypertension (HTN) is a leading risk factor of cardiovascular diseases. Its pathogenesis is poorly understood, but activation of the renin angiotensin system is thought to be a key event. Vascular damage is an early manifestation of HTN. There are currently no available clinical biomarkers for early detection of vascular damage. Circulating microvesicles (MVs) have gained significant attention as potential novel biomarkers for vascular injury. These vesicles are less than 1 micron in size and carry markers of the parent cell. We hypothesized that MVs of endothelial and leukocyte origin are elevated in angiotensin II (AII) induced-HTN and show a distinct phenotype depending on the duration of HTN. Methods: Mice were treated with AII (400ng/kg/min) via mini-osmotic pumps for 2 and 4 weeks (wks). Systolic blood pressure (SBP) was measured using tail-cuff manometry. Enumeration and phenotyping of MVs were determined in platelet poor plasma using imaging flow cytometry and the following surface markers: E- Selectin (CD62E), Endoglin (CD105), VE Cadherin (CD144), Annexin 5 (AV), Platelets (CD41), P-Selectin (CD62E), leukocytes (CD45). Results: Compared to untreated controls (n=5), AII treated mice (n=5) had an increase in SBP by 30mmHg (p=0.02), and significantly elevated total counts of AV negative (AV-) and positive MVs (AV+) (p=0.04 and 0.06 respectively) after 2 wks. Endothelial derived MVs were also significantly elevated after 2 wks (AV+ and AV- CD144+ (p=0.023), AV+ and AV-CD62E+ (p=0.023), AV+ and AV-CD105+ (0.023), AV+ and AV- CD144+ (p=0.04)). However, after 4 wks of AII-induced HTN, only AV-CD144+ MVs remained significantly elevated. In contrast, leukocyte derived MVs (CD45+) were significantly increased after 2 wks, and remained significantly elevated after 4 wks. Platelet derived MVs were not significantly elevated at either time point. Conclusions: Distinct populations of endothelial and leukocyte derived MVs are elevated at different time points during AII-induced HTN. The changing profiles of the MVs may reflect an evolving pathophysiologic response of the vasculature. Further studies are needed to confirm these findings, and to determine the effect of the severity and etiology of HTN on the profiles of MVs.