The development of microvascular complication in diabetes is particularly related to the classic risk factors, like hypertension and dyslipidaemia, several factors play a role in the accelerated atherosclerosis observed in diabetic patients, such as metabolic disorder, endothelial dysfunction, increased propensity for thrombosis and impaired fibrinolysis, and increased platelet aggregation (Knobler et al., 2004).
Platelets play a major role in the hemostatic process, and increased platelet activation and aggregation are the center of the pathophysiology of arterial thrombosis (Freedman and Loscalzo, 2002).
Platelet-monocyte aggregates play an important role in the development of microvascular disease and atheromatous lesions. Increased numbers of circulating pro-inflammatory monocytes, circulating activated platelets, and/or circulating leukocyte- platelet aggregates have been observed in patients with diabetes mellitus (Methe et al., 2005 and Devaraj et al., 2006).
Circulating platelet-monocyte aggregates formed by the binding of activated platelets to leukocytes via a P-selectin dependent mechanism , which can be readily measured and considered as a highly sensitive marker of platelet activation (Michelson et al., 2001).
Upon activation, the degranulated platelets rapidly express P-selectin (CD62P) which is a component of the α-granule of resting platelets and expressed only on the platelet surface membrane after α-granule secretion, and adhere to leukocytes, mainly by interacting with P-selectin glycoprotein ligand-1 (PSGL-1), This initial association leads to increased expression of CD11b/CD18 (Mac-1) on leukocytes, which itself supports interactions with platelets, perhaps because bivalent fibrinogen links this integrin with its platelet surface counterpart glycoprotein IIb/IIIa. This leads to the formation of heterotypic leukocyte- platelet aggregates which might trigger inflammatory responses at vascular injury sites ( Graff et al ., 2001).
The purpose of the present study was to investigate whether the circulating PMA levels were increased in diabetic patients and if they may be correlated to the vascular damage, currently observed in diabetes.
In the current study we examined platelet – monocyte aggregates in 15 apparently healthy normal persons as control group A, 19 diabetic patients without microvascular injuries as control group B and 59 microvascular injured diabetic patients as group C. All these groups were subjected to full medical history taking, thorough clinical examination, complete blood counts, cholesterol, T.G, serum creatinine, Hb A1c and detection of CD14 (monocyte marker) and CD 41(platelet marker) by Flow Cytometry (FCM).
In the present study, there was significant increase of PMA% in diabetic patients than control group A, and there was also significant increase of PMA% in group C than Group B.
The current study also showed that, significant positive correlation between PMA% and glycemic state of diabetic patients, represented by HbA1c level, and significant positive correlation between PMA% and lipid state of patients (cholesterol and T.G).
Conclusion:
Circulating PMA determination by flow cytometry may be used as a simple marker of microvascular injury in diabetic patients. Indeed, a relationship was established between the increased circulating PMA, and the incidence of microvascular injury seen in diabetic patients. Besides, our data reinforce the concept involving the pro-inflammatory cells and their cooperation with platelets in pathogenesis of diabetic microvascular complication.
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