Abstract 55: Spatiotemporal Heterogeneity of Platelet Activation and Thrombus Architecture Regulates Plasma Protein Accessibility During Thrombus Formation in Vivo
While often described as a linear process in which platelets react in a uniform manner, recent in vivo studies demonstrate that the platelet response to vascular injury is quite heterogeneous. Here, we utilized confocal fluorescence intravital microscopy to provide a detailed description of the heterogeneous nature of thrombi formed in vivo while asking the following questions: 1) does platelet accumulation and activation during thrombus formation follow specific spatio-temporal patterns that result in subpopulations of platelets with different activation states; 2) does the architecture of the hemostatic mass depend on the mechanism of injury; and 3) does heterogeneity within the platelet mass result in discrete regions of a thrombus that are more or less accessible to plasma and its constituents? We found that regardless of the mode of injury, stable thrombi were composed of two distinct and contiguous populations of platelets defined both by their activation state and their packing density. Closest to the site of injury was a population of fully activated, stably adherent, degranulated platelets, which was covered by multiple layers of loosely adherent platelets that had not undergone granule release. Increased packing density of platelets within the thrombus core was associated with reduced plasma volume in this region as well as limited accessibility of large plasma borne tracer molecules and proteins. Taken together, these findings clearly demonstrate the heterogeneous nature of thrombus formation at the molecular and structural levels. Further, the finding of reduced plasma volume and protein accessibility to the thrombus core has implications for delivery of pro- and anti-thrombotic blood factors and therapeutic agents to this region of a thrombus.
- © 2012 by American Heart Association, Inc.