Vascular endothelial growth factor, lipoporotein-associated phospholipase A2, sP-selectin and antiphospholipid antibodies, biological markers with prognostic value in pulmonary hypertension associated with chronic obstructive pulmonary disease and systemic lupus erithematosus.

OBJECTIVE: Pulmonary arterial hypertension (PH) is a progressive disease with a poor prognosis that ultimately leads to right ventricular failure and death. The pathogenesis of severe PH seems to be related to inflammatory responses and coagulation disturbances. Many diseases can develop PH in their course, thus aggravating their outcome. The objective was to investigate the values of vascular endothelial growth factor (VEGF), sP-selectin, lipoprotein-associated phospholipase A2 (PLA2-LDL), antiphospholipid antibodies (APLA) and their relation with PH, in systemic lupus erythematosus (SLE) and chronic obstructive pulmonary disease (COPD), two conditions in which the occurrence of PH is frequent. DESIGN: Prospective clinical study. SETTING: A University Department of Internal Medicine, a National Institute of Research. PATIENTS: 30 SLE patients (15 patients without PH (group I) and 15 patients with PH group II)), 30 patients with COPD (15 patients without PH (group III) and 15 patients with PH (group IV)) and 10 healthy controls, selected by clinical, immunological, echocardiographical criteria and pulmonary functional tests. MAIN OUTCOME MEASURES: VEGF, sP-selectin and PLA2-LDL level in plasma and presence of antiphospholipids antibodies (lupus anticoagulant, anticardiolipin and anti beta2 GPI) in plasma. - RESULTS: In patients with PH, the values of VEGF were significantly increased [group II (1023.1) and IV (904.3)] compared with group I (744.2), III (356.4), and controls (330.3). The values of sP-selectin in group II (9.7), and IV (10.4) were also increased compared with controls (6). APLA were present in all patients in group II (100%), and in 8 patients in group IV (53%), while in the other groups the frequency was low (33% group I and 13% group III). PLA2-LDL activity was higher in group II (429.1) and group IV (394.5) than in group I (317.8), group III (343.2) and controls (256.3). CONCLUSION: PH is a severe complication in COPD and SLE. The increased values of VEGF, PLA2-LDL and P-selectin in patients with long standing PH are related to severe endothelial dysfunction and may have prognostic values. APLA may have pathogenic value in SLE patients with PH. APLA are possibly implicated in the pathogenesis of PH in these diseases. VEGF, APLA and sP-selectin may constitute new therapeutic targets for PH.

The in vitro effect of a low molecular weight heparin, nadroparin (Fraxiparine), on leukocytes obtained from patients with vascular diseases.

BACKGROUND: Both lymphocytes and granulocytes may play a role in the immune system-mediated inflammatory response associated with non-Q wave infarction and aortic aneurysms. METHODS: The purpose of this study was to establish the in vitro effects of a low molecular weight heparin (LMWH), nadroparin (Fraxiparine), on some functional parameters of peripheral granulocytes and lymphocytes isolated from control subjects and patients with aortic aneurysm or non-Q wave infarction. RESULTS: Nadroparin (0.06-600 AXaU/ml) exerted different in vitro effects on granulocytes and lymphocytes isolated from normal subjects and the patient groups. The following indices were assessed: superoxide anion release, lymphocyte proliferation, phagocytic activity and the cellular respiratory burst. The effects of nadroparin varied according to the patient group and the index of lymphocyte/granulocyte assessed. CONCLUSIONS: Since peripheral granulocytes isolated from these patients are activated, the observed inhibition exerted by nadroparin on superoxide anion release may be beneficial. LMWHs have additional effects that are independent of their anticoagulant activity. These effects may influence the "inflammatory component" of the atherosclerotic process.

Familial lupus anticoagulant.

The antiphospholipid antibody syndrome (APS) is defined by widespread arterial and venous thromboses associated with elevated plasma levels of antiphospholipid antibodies (APLA). The primary antiphospholipid antibody syndrome (PAPS) appear to be a fairly homogeneous disease, and HLA, family and other studies provide new insights into this cause of thrombosis and vascular disease. We describe two patients with PAPS (lupus anticoagulant positive), whose family members were analyzed for clinical and laboratory abnormalities associated with APS. Familial screening seems to be important, in order to prevent the thrombotic events. Low dose aspirin is the first line treatment in asymptomatic subjects with APLA, previous or present thrombosis requiring long-term, possibly life-long anticoagulation.

Peripheral leukocytes activation in aortic aneurysmal disease.

The pathogenesis of aneurysmal disease involves factors acting over time. A sustained chronic inflammatory reaction is observed in association with initiations, maintenance, rapid growth and rupture of aortic aneurysms. This study was designed to identify the possible pathogenic role of the inflammatory cells in the outcome of aneurysmal disease, testing the activation state of peripheral lymphocytes and neutrophils. Circulating activated lymphocytes and repeated peaks of neutrophils activation in sequential follow-up is associated with larger aneurysms, mural thrombosis, tendency to aneurysm extension and rupture.