Serum from patients with acute coronary syndromes displays a proapoptotic effect on human endothelial cells: a possible link to pan-coronary syndromes.
BACKGROUND
Endothelial apoptosis of atherosclerotic lesions is a possible determinant for the stable-to-vulnerable plaque transition. Recent data support the notion that plaque activation may be a pan-coronary process, advocating the existence of circulating triggers.


RESULTS
Serum from 40 healthy subjects (group 1) and 73 patients with stable angina (n=32; group 2) or acute coronary syndromes (n=41; group 3) was incubated with human umbilical vein endothelial cells. The percentage of apoptosis by flow cytometry and Fas, Bax, and Bcl-2 protein expression by immunoblotting were evaluated at entry in patients and control subjects and repeated after 12 months in group 3. At baseline, apoptotic nuclei were higher in group 3 (14+/-6%) than in group 2 (3.3+/-1.8%) and group 1 (1.35+/-0.8%) (P<0.001). Fas and Bcl-2 were increased in group 3 with respect to groups 1 and 2 (P<0.01). Coincubation of group 3 serum with anti-tumor necrosis factor-alpha and anti-interleukin-6 monoclonal antibodies did not affect the human umbilical vein endothelial cell apoptotic process, whereas addition of Trolox decreased apoptosis to <50%. The percentage of apoptosis in group 3 significantly correlated to the numbers of coronary complex lesions at angiography (r=0.58, P<0.0005). In group 3, apoptosis and the Bax/Bcl-2 ratio decreased at 1 year (P<0.0001, P<0.05 respectively).


CONCLUSIONS
Serum from patients with acute coronary syndromes displays a proapoptotic effect on human endothelial cells, supporting the theory of the existence of circulating triggers potentially able to activate atherosclerotic lesions.
Valgimigli
Marco
M
Department of Cardiology, University of Ferrara, Ferrara, Italy.
Agnoletti
Laura
L
Curello
Salvatore
S
Comini
Laura
L
Francolini
Gloria
G
Mastrorilli
Francesca
F
Merli
Elisa
E
Pirani
Roberto
R
Guardigli
Gabriele
G
Grigolato
Pier Giovanni
PG
Ferrari
Roberto
R
D000208:Acute Disease; D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000175:diagnosis; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000097:blood; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001798:Blood Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000096:biosynthesis; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000975:Antioxidants; D001798:Blood Proteins; D002839:Chromans; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D000093242:Interleukin-6 Inhibitors; C494826:BAX protein, human; C507763:IL1RN protein, human; C099252:oxidized low density lipoprotein; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid