Evidence of Endothelial Dysfunction in Cocaine Users.

Background: Cocaine abuse is associated with an increased risk of cardiac and cerebrovascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation and accelerated atherosclerosis are prominent findings. In this sense, in vitro studies have demonstrated that cocaine may induce damage and/or activation of endothelial cells. The structural and functional integrity of the endothelium is essential for the maintenance of vascular homeostasis and its damage plays a critical role in the pathogenesis of vascular disease. Endothelial dysfunction may be assessed by testing the impaired vasodilator response to a stimulus or by measuring the release of plasma markers of endothelial damage. Increased number of circulating endothelial cells (CECs) has been reported in several pathologic conditions associated with severe vascular damage and its enumeration in peripheral blood is currently considered a reliable method to assess endothelial damage. We hypothesized that chronic exposure to cocaine induces endothelial damage which could be expressed by increased CEC counts in peripheral blood. Methods: Twenty cocaine-dependent subjects (aged 19–52 years, mean age 30 years) and 25 healthy, matched controls (aged 20–49 years, mean age 31 years) were studied; all patients fulfilled DSM-IV criteria for cocaine dependence with drug exposure within the 72 hours prior to blood sampling. CECs were isolated from peripheral blood by use of immunomagnetic beads coated with anti-CD146, stained for CD45 and Ulex Europaeus lectin 1 and counted under fluorescence microscopy. MCP-1, sICAM-1, von Willebrand factor and high-sensitivity C-reactive protein (hsCRP) were measured by enzyme-linked immunosorbent assay. Results: Compared to controls, CECs were significantly elevated among cocaine users (632 ± 281 vs 67 ± 54 cells/mL, p<0.0001). Plasma levels of sICAM-1 (360±92 ng/mL) and MCP-1 (166±71 pg/mL) were increased in cocaine-dependent individuals compared to the controls (261±34 and 67±29, respectively; p< 0.01). The hsCRP levels were significantly increased (6.8 mg/L); however plasma von Willebrand factor concentration was not different between patients and controls (86.4±22 vs 70.5±16%, respectively; NS). Levels of CECs correlated positively with sICAM-1 (r: 0.7; p: 0.003) and hsCRP (r: 0.56; p: 0.0037). Conclusions: Highly increased number of CECs and significant increments in soluble plasma markers of endothelial perturbation were found in cocaine dependent individuals. This is the first demonstration of endothelial dysfunction among these individuals and our findings support the notion that cocaine-induced endothelial damage may play a pathogenic role in the ischemic vascular disease observed in chronic cocaine users.