Abstract

Despite the significant deleterious impact of hypertension (HTN), the blood pressure (BP) threshold at which to treat remains a matter of debate. Early and non-invasive biomarkers of end-organ damage in HTN are needed to optimize treatment for patients with HTN. Circulating microparticles (MPs) are potential candidate biomarkers to reflect early end-organ damage in HTN. MPs are submicron vesicles shed from various cell types in the blood and carry markers from their parent cells. We hypothesize that these MPs show a distinct pattern during evolution of HTN in spontaneous hypertensive rats (SHR), a model of essential HTN. MPs were generated from platelet poor plasma from tail vein of SHR before development of HTN (7 weeks (wk) of age), at time of development (9 wk) and severe HTN (12 wk). WKY rats served as control. Enumeration and phenotyping of MPs was performed with imaging flow cytometry using CD42 (platelet marker), CD31 (PECAM), CD105 (S-endoglin), CD45 (leukocyte) and Annexin V (AnV) as surface markers. Compared to WKY (n=3), aII SHR (n=3) had a significant increase in systolic BP by 40mmHG (by radiotelemetry) (p=0.02). All types of MPs increased at wk 9 compared to wk 7 and then decreased again at wk 12 in both groups. However, the increase of MPs was numerically higher in a subgroup of endothelial MPs in SHR after 12 wk compared to controls (AnV negative and S-endoglin (CD105) positive, median 34333 vs 10328 MPs/μl plasma, p=0.08). Subgroups of circulating MPs show a distinct pattern in the SHR. It remains to be determined whether these vesicles reflect early end-organ damage in HTN and have the potential to guide treatment.

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