TY - JOUR
T1 - Simvastatin reduces platelet-endocardium adhesion in atrial fibrillation
AU - Chello, Massimo
AU - Spadaccio, Cristiano
AU - Patti, Giuseppe
AU - Lusini, Mario
AU - Barbato, Raffaele
AU - Goffredo, Costanza
AU - Di Sciascio, Germano
AU - Covino, Elvio
PY - 2008/4
Y1 - 2008/4
N2 - Objectives: 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 μM 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.
AB - Objectives: 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 μM 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.
KW - Atrial fibrillation
KW - CD40
KW - Platelets
KW - Statin
UR - http://www.scopus.com/inward/record.url?scp=40949157019&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2007.08.021
DO - 10.1016/j.atherosclerosis.2007.08.021
M3 - Article
SN - 0021-9150
VL - 197
SP - 588
EP - 595
JO - Atherosclerosis
JF - Atherosclerosis
IS - 2
ER -