PRESENCE OF AUTOANTIBODIES AGAINST OXIDATIVELY MODIFIED LOW-DENSITY-LIPOPROTEIN IN ESSENTIAL-HYPERTENSION - A BIOCHEMICAL SIGNATURE OF AN ENHANCED IN-VIVO LOW-DENSITY-LIPOPROTEIN OXIDATION

Objective: We have previously reported that low-density lipoproteins ( LDL) isolated from patients with essential hypertension are more susce ptible to in vitro oxidation than lipoproteins isolated from normotens ive control subjects. In the present study we investigated the occurre nce of in vivo LDL oxidation in hypertensive patients. Design: The pre sence of antioxidatively modified LDL autoantibodies was taken as a su itable index of in vivo LDL oxidation because, after oxidative modific ations, LDL express antigenic epitopes that elicit an immune response. The antibody titres were measured in plasma from untreated patients w ith newly diagnosed essential hypertension. Methods: An enzyme-linked immunosorbent assay method was employed, using native LDL, Cu2+-oxidiz ed LDL and malondialdehyde-derivatized LDL (MDA-LDL) as antigens. Huma n serum albumin and MDA human serum albumin were also used to monitor cross-reactivity with other oxidized molecules. The antibody titre was expressed as the ratio between anti-modified and anti-native antigen absolute values. Results: The patients with essential hypertension had an antibody ratio significantly higher than control subjects with res pect to anti-Cu2+-oxidized LDL immunoglobulins G and M, and with respe ct to anti-MDA-LPL immunoglobulins G and M. A significant positive cor relation was found between anti-MDA-LDL and anti-Cu2+-oxidized LDL ant ibody titres. The anti-MDA human serum albumin antibody titre was not different in the two groups of patients. An inverse correlation was de tected between the anti-MDA-LDL immunoglobulin M titre and the age of the patients. Conclusions: The results obtained are consistent with th e view that, during the early phases of hypertension development, LDL undergo in vivo oxidation that is mirrored by the generation of autoan tibodies against epitopes of oxidized LDL. The oxidation process appea rs specific for LDL and might be relevant both for the progression of hypertension and for the development of the atherosclerosis that often complicates hypertension itself.