In vivo platelet activation is responsible for enhanced vascular endothelial growth factor levels in hypertensive patients

BACKGROUND: Essential hypertension may be a consequence of an abnormal regulation of vascular endothelial growth factor (VEGF). In vivo activation of platelets does result in the release of VEGF. Thus, we investigated whether VEGF production in hypertensive patients is related to in vivo platelet activation, and whether it may be modified by aspirin treatment. METHODS: Plasma VEGF, soluble (s)P-selectin and thrombin-anti-thrombin complex (TATc) were analyzed in 80 patients with therapeutically controlled essential hypertension and 40 age and sex-matched healthy normotensive controls. The effects of a 6-month treatment with aspirin 100 mg/day on VEGF levels of 20 hypertensive patients were also studied. RESULTS: Plasma VEGF (p<0.0001), sP-selectin (p=0.01) and TATc (p=0.02) levels were higher in hypertensives compared to controls. Multivariate analysis including age, sex, risk factors, cardiovascular disease, anti-hypertensive treatment, sP-selectin and TATc showed that only sP-selectin was an independent predictor of VEGF (beta=0.40, p<0.03). Aspirin treated hypertensives showed a significant reduction of sP-selectin (-26%, p<0.01) and VEGF (-33%, p<0.01) levels. Moreover, the reduction of plasma VEGF levels directly correlated with that of sP-selectin (Rho=0.46, p=0.04). CONCLUSIONS: In vivo activation of platelets in hypertensive patients is responsible for enhanced circulating VEGF levels, which are significantly lowered by aspirin treatment.