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Platelet P‐selectin mediates cytomegalovirus‐induced microvascular dysfunction
Author(s) -
Stokes Karen,
Leskov Igor L,
Senchenkov Evgeny V
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.589.13
Subject(s) - platelet , p selectin , inflammation , platelet activation , immunology , cytomegalovirus , population , endothelial dysfunction , medicine , endocrinology , chemistry , herpesviridae , virus , environmental health , viral disease
Cytomegalovirus (CMV) infects a majority of the population worldwide. It has been implicated in cardiovascular disease (CVD) possibly through its inflammatory actions. Although platelets and platelet‐associated P‐selectin (P‐sel) are linked to inflammatory responses in CVD, their role in CMV‐induced vascular responses is unknown. We assessed the role of platelets in CMV‐induced microvascular inflammation. Wildtype (WT) mice and bone marrow chimeric mice deficient in platelet P‐sel (P‐sel Ch) received mock or murine CMV (mCMV) IP. Mice were fed normal chow (ND) or placed on high cholesterol diet (HC) at 5wk p.i. to investigate the synergism between mCMV & HC. Microvascular responses were measured at 11wk. Some WT mice were depleted of platelets 24h before observation. mCMV−/+HC caused significant endothelial dysfunction in arterioles. Vasodilation in mCMV‐ND P‐sel Ch, but not platelet depleted mice, was restored to Mock‐ND levels. Partial protection was seen in mCMV+HC mice with platelet depletion or in P‐sel Ch. Only mCMV+HC elevated leukocyte recruitment in venules. This was reduced to mock levels by acute platelet depletion, but not in P‐sel Ch. Our findings implicate a novel role for platelets, acting through P‐sel, in CMV‐induced arteriolar dysfunction, and suggest that the addition of HC leads to a platelet‐dependent, P‐sel independent inflammatory infiltrate. (AHA‐0730294N & NIH‐P20RR018724)