Summary
CD40 and its ligand (CD40L) are glycoproteins from the tumor necrosis factor family (Freedman, 2003). The CD40–CD40 ligand system is widely distributed on a variety of leukocytic and nonleukocytic cells, including endothelial and smooth-muscle cells, (Schonbeck et al., 2001) and on activated platelets, (Henn et al., 1998).
CD40 ligand also occurs in a soluble form that is fully active biologically, termed soluble CD40 ligand which is shed from stimulated lymphocytes and is actively released after platelet stimulation ( Henn et al., 2001).
Soluble CD40 ligand is proinflammatory for endothelial cells and promotes coagulation by inducing expression of tissue factor on monocytes and endothelial cells (Urbich et al., 2001).Moreover, soluble CD40 ligand contains a KGD )Lys-Gly-Asp) sequence, a known binding motif that is specific for the major platelet integrin aIIbβ3 (Graf et al., 1995).
Indeed, CD40 ligand has been demonstrated to be an aIIbβ3 (glycoprotein IIb/IIIa) ligand and a platelet agonist and to be necessary for the stability of arterial thrombi (Andre et al., 2002a).
The aim of this work was to evaluate levels of sCD40L in smokers with acute MI versus non-smokers to identify the patients who are likely to benefit from treatment with the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonists.
The present study was conducted on 79 subjects, 59 males and 20 females since April 2012 to May 2013, subdivided into two groups.
Group I: This group included 60 patients with AMI (ST segment elevation and non-ST segment elevation), including 45 males and 15 females and have been admitted to Coronary Care Unit in Benha University Hospital.
Exclusion criteria:
1- Those patients with acute MI onset > 24 h, or age > 60 years.
2- Patients with history of Percutaneous Coronary Intervention (PCI), or coronary artery bypass graft surgery.
3- Patients with diabetes mellitus, dyslipidaemia, atrial fibrillation, renal or hepatic failure, significant valvular abnormalities, chronic obstructive pulmonary disease, active inflammatory or connective tissue diseases, malignancy ,febrile disorders, cardiogenic shock patients requiring intraaortic balloon pump therapy, patients with a history of recent surgery or trauma within the preceding 2 months .
4- Patients receiving antiplatelet agents such as acetylsalicylic acid and clopidogrel for any medical reason. Also, the patients that were given these agents and heparin during transfer to the hospital were excluded.
Inclusion criteria:
1- Patients of both genders with age range (40 – 60) years with acute MI defined as having symptoms of ischemia that were verified by electrocardiography or by increased levels of biochemical markers (Creatine Kinase-MB isoenzyme [CK-MB], >25U/L [25U/L] or troponin I [TnI], >0.1 μg/L [0.1 ng/mL]) (Apple et al., 1995).
2- Patients who were undergoing primary Percutaneus Coronary Intervention were included in the study.
Group II: This group included nineteen apparently healthy individuals of matched age and sex. They were 14males & 5 females
Both groups were further subdivided into 2 subgroups:
A- Smokers group defined as those currently smoking any type of tobacco in more than ten cigarettes per day and ex-smoker patients were excluded from the study.
B- Non-smokers group.
All individuals in the study were subjected to the following:
1- Full history taking paying attention to:
* Name, Age and date of admission.
* Risk factors:
* Smoking, number of cigarettes per day
*History of chest pain.
2- Chest pain was confirmed with E.C.G. or diagnostic coronary angiography findings.
3- Laboratory investigations which included:
A) Routine Laboratory Investigations:
* Fasting blood glucose level
* Liver Function Tests (Alanine Transaminase, Aspartate Transaminase, Total Bilirubin, Albumin and Prothrombin Time).
* Kidney Function Tests (Urea and Creatinine).
* Lipid Profile (Total Cholesterol, High-denisty Lipoprotein Cholesterol, Low-denisty Lipoprotein Cholesterol and Triglycerides).
B) Specific Laboratory Investigations:
* Cardiac markers: CK-MK and Troponin I.
* High sensitive C-reactive protein (CRP) using a specific en-zyme-linked immunosorbent assay (ELISA) kit.
* The concentration of soluble CD40L levels in plasma using a specific enzyme-linked immunosorbent assay (ELISA) kit.
The results of this work were summarized as the following:
There is a statistically highly significant increase in the mean sCD40L and HS-CRP concentration in patient group versus control group.
There is a statistically significant increase in the mean sCD40L and HS-CRP level in smokers versus non-smokersand in patients with STEMI versus patients with NSTEMI.
There is a significant positive correlation between HS-CRP and sCD40L.
Multiple stepwise regression analysis was done using elevated sCD40L level as well as elevated HS-CRP as dependent factors and smoking status, type of MI as independent factors. It was found that smoking status is a significant independent predictor for elevation of both sCD40L and HS-CRP levels.
So this study demonstrated that the circulating levels of sCD40L are increased in smokers during the early phase of acute MI.
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