Abnormal angiopoietins 1&2, angiopoietin receptor Tie-2 and vascular endothelial growth factor levels in hypertension: relationship to target organ damage [a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)]

Background. The increased risk of target organ damage (TOD) in hypertension may be related to a prothrombotic or hypercoagulable state, with abnormalities in platelet activation. Altered angiogenesis, possibly related to increased plasma vascular endothelial growth factor (VEGF) is also a feature of hypertension. We hypothesized a link between altered angiogenesis and TOD in hypertension. Accordingly, the angiogenic growth factors VEGF, angiopoietin 1 and 2 (Ang 1 & 2) and soluble angiopoietin receptor Tie-2 in plasma and in platelets were assessed in terms of the presence or absence of hypertensive TOD. Methods. We studied 199 patients (75% men; mean age 68 years) with hypertension. Of these, 125 had evidence of hypertensive TOD (stroke, previous myocardial infarction, angina, left ventricular hypertrophy and mild renal failure). Patients were compared with 74 healthy normotensive controls (69% men; mean age 68 years). Plasma VEGF, Ang 1 & 2 and Tie-2, and total platelet levels of VEGF and Ang-1 (obtained by lysing a known number of platelets with 0.5% Tween) were measured by an enzyme-linked immunosorbent assay. Results. Hypertensive patients had higher levels of plasma VEGF, Ang-1, Ang-2, Tie-2 and platelet VEGF (all P <= 0.01), but not platelet Ang-1, when compared with normotensive controls. Patients with TOD had higher levels of platelet VEGF and Ang-1 (both P < 0.001), and plasma Ang-1 (P < 0.001). Amongst the hypertensives, plasma levels of VEGF correlated significantly with Ang-1, Ang-2, Tie-2 and platelet VEGF, whilst platelet VEGF correlated strongly with plasma levels of VEGF and Ang-1 (all P < 0.05). Conclusion. Patients with hypertension have evidence of changes in plasma angiogenic growth factors that correlate with the platelet levels of these molecules. Platelets may be involved in the abnormal angiogenesis seen in hypertension.