Simvastatin reduces platelet-endocardium adhesion in atrial fibrillation.
OBJECTIVE
To evaluate the relationship between CD40/CD40L system and increased thrombogenesis in AF, and to test the effects of simvastatin treatment.


METHODS
In vitro study using human tissue, University Hospital (tertiary referral center). Experiments on right atrial segments obtained before the onset of cardiopulmonary bypass were done in either presence or absence of 5 microM simvastatin. Two groups of patients in either chronic atrial fibrillation or sinus rhythm at the time of cardiac surgery. The endocardial expression of CD40, the release of CD40L, and adhesion of platelets to endocardium. Additionally, the thickness of platelet aggregates and the platelet distribution on the endocardium were also evaluated.


RESULTS
Atrial fibrillation was associated with a significant increase of endocardial CD40 expression (293.1+/-55.1 pg/ml vs. 230.9+/-53.3 pg/ml, p<0.01), and platelet-endocardial adhesion compared with sinus rhythm atria (10.8+/-2.2 vs. 5.2+/-1.3 platelet CD41 AU p<0.01). At immunofluorescence about 62% of fibrillating endocardium was covered by platelets, compared with 12% of not sinus rhythm atria. Addition of simvastatin significantly reduced CD40 expression as well as platelet adhesion to fibrillating atria; its efficacy was not reversed by the addition of mevalonic acid.


CONCLUSIONS
Chronic atrial fibrillation acutely upregulates CD40 expression as well as platelet adhesion to the endocardium. Simvastatin is effective in modulating this expression, thus it may potentially contribute to reduce the risk of intra-atrial thrombus formation.
Chello
Massimo
M
Interdisciplinary Center for Biomedical Research (CIR), Department of Cardiovascular Sciences, University Campus BioMedico of Rome, Italy. m.chello@unicampus.it
Spadaccio
Cristiano
C
Patti
Giuseppe
G
Lusini
Mario
M
Barbato
Raffaele
R
Goffredo
Costanza
C
Di Sciascio
Germano
G
Covino
Elvio
E
D000368:Aged; D001281:Atrial Fibrillation / Q000378:metabolism / Q000503:physiopathology*; D016280:Atrial Function, Right; D019013:CD40 Antigens / Q000187:drug effects / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D016022:Case-Control Studies; D004699:Endocardium / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006325:Heart Atria / Q000503:physiopathology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010973:Platelet Adhesiveness / Q000187:drug effects*; D019821:Simvastatin / Q000494:pharmacology*
D019013:CD40 Antigens; D023201:CD40 Ligand; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases