Microvesicles at the crossroads between infection and cardiovascular diseases

Abstract

Observational and experimental studies continue to support the association of infection and infection-stimulated inflammation with development of cardiovascular disease (CVD) including atherosclerosis and thrombosis. Microvesicles (MV) are heterogeneous populations of sealed membrane-derived vesicles shed into circulation by activated mammalian cells and/or pathogenic microbes that may represent an interface between bacterial/microbial infection and increased risk of CVD. This review evaluates how MV act to modulate and intersect immunological and inflammatory responses to infection with particular attention to progression of CVD. Although infection-related stimuli provoke release of MV from blood and vascular cells, MV express phosphatidylserine and other procoagulant factors on their surface, which initiate and amplify blood coagulation. In addition, MV mediate cell-cell adhesion, which may stimulate production of pro-inflammatory cytokines in vascular cells, which in turn aggravate progression of CVD and propagate atherothrombosis. MV transfer membrane receptors, RNA and proteins among cells, and present auto-antigens from their cells of origin to proximal or remote target cells. Because MV harbor cell surface proteins and contain cytoplasmic components of the parent cell, they mediate biological messages and play a pivotal role in the crossroad between infection-stimulated inflammation and CVDs.

Figure 1

ATP secretion in response to thrombin (0.1 U/mL) (black bars) and platelets associated with leukocyte-derived MV (gray bars) after whole blood from mice was incubated with LPS (5 μg/mL) or saline (control) for 1h. P<0.01 vs. Control.

Figure 2

Schematic of how MV of gram-negative bacteria may interface with host cells to increase progression of cardiovascular disease.