Increased plasma levels of the soluble form of Fas ligand in patients with acute myocardial infarction and unstable angina pectoris.
OBJECTIVE
To examine whether the Fas/Fas ligand system is involved in the pathogenesis of acute myocardial infarction (AMI), we measured the levels of the soluble form of the Fas ligand (sFasL) in the plasma of patients with AMI and stable or unstable angina pectoris (AP).


BACKGROUND
The Fas ligand (FasL) is rapidly cleaved off by a metalloproteinase from the cell membrane to become a soluble form as a cytokine. Fas is expressed in most cells, including cardiomyocytes, whereas FasL is mainly expressed in inflammatory cells such as macrophages, which are greatly accumulated in unstable plaque.


METHODS
Thirty patients with AMI, 10 patients with unstable AP, 10 patients with stable AP and 30 control subjects were enrolled in the present study.


RESULTS
Plasma sFasL levels were significantly elevated on hospital admission in patients with AMI and unstable AP, compared with control subjects. Time-course studies revealed that plasma sFasL levels rapidly decreased within 3 h and then increased again after percutaneous transluminal coronary angioplasty in patients with AMI, but not in patients with stable AP. Importantly, the sFasL levels were higher in the coronary sinus than in the circulation. In addition, in vitro studies showed that the expression of FasL messenger ribonucleic acid was upregulated in mononuclear cells isolated from patients with AMI and that hypoxia stimulated the release of sFasL from isolated mononuclear cells.


CONCLUSIONS
This demonstration of elevated levels of sFasL in patients with AMI and unstable AP suggests that activation of the Fas/FasL system may play a pathogenic role in AMI and acute coronary syndromes.
Shimizu
Masumi
M
Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
Fukuo
Keisuke
K
Nagata
Shigekazu
S
Suhara
Toshimitsu
T
Okuro
Masashi
M
Fujii
Kenshi
K
Higashino
Yorihiko
Y
Mogi
Masaki
M
Hatanaka
Yasuko
Y
Ogihara
Toshio
T
D000368:Aged; D000787:Angina Pectoris / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D000789:Angina, Unstable / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D017023:Coronary Angiography; D053222:Fas Ligand Protein; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012720:Severity of Illness Index; D012995:Solubility; D013997:Time Factors
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins