Upregulation of the immune system in primary hypercholesterolaemia: effect of atorvastatin therapy

Abstract

Sampietro T, Bigazzi F, Rossi G, Dal Pino B, Puntoni MR, Sbrana F, Chella E, Bionda A (CNR Institute of Clinical Physiology, Pisa; and University of Pisa, Pisa; Italy). Upregulation of the immune system in primary hypercholesterolaemia: effect of atorvastatin therapy. J Intern Med 2005; 257: 523-530.Objectives. High levels of plasma high sensitivity Creactive protein (CRP), sensitive to therapy with statins, have been described in hyperchole sterolaemia. In vitro evidence shows that CRP activates the complement system, which, in turn, leads to an increased expression of ICAM-1. Our objectives were to verify whether primary hypercholesterolaemia (PHC) is associated with an upregulation of the inflammatory/immune response, and whether this is sensitive to atorvastatin. Methods and results. We examined the levels of sICAM-1, C3, C4 complement fractions in 48 patients with PHC, with (CAD group) or without (No-CAD group) coronary artery disease (CAD) in comparison with a group of 48 healthy controls. The two patient groups were studied before and after atorvastatin therapy. Both hypercholesterolaemic groups showed higher mean values of sICAM-1, C3 and C4 (P < 0.0001) when compared with the controls. The two groups of patients responded differently to atorvastatin therapy. After 3 months, the C3 levels normalized in both groups of patients (P < 0.02 compared with basal values); C4 was greatly reduced only in the CAD group (P < 0.01). After 12 months of therapy, in CAD group C3 mean levels were still significantly lower than baseline values (P < 0.01); a further decrease in the C4 values (P < 0.05 with respect to levels after 3 months of therapy) and also a substantial reduction in sICAM-1 values (P < 0.001 with respect to basal values) were observed. Conclusions. High plasma values of C3 and C4 in PHC cluster with high values of sICAM-1, distinguish subjects with CAD and could be used to monitor the anti-inflammatory effect of statin therapy in these patients.

Complement regulation in murine and human hypercholesterolemia and role in the control of macrophage and smooth muscle cell proliferation

“…High plasmatic C3 and C4 levels have been reported in individuals with primary hypercholesterolemia [37], and increased circulating level of C5b-9, a clear indicator of complement activation, is associated with human dyslipidemias, including hypercholesterolemia, hypertriglyceridemia and low HDL-cholesterol level [38]. These findings are consistent with the observation that cholesterol, modified LDLs, and chylomicrons represent complement-activating lipids [6,7,39,40].…”

Nutrigenomic analysis of the protective effects of bilberry anthocyanin-rich extract in apo E-deficient mice

“…It is involved in the complement system activation, associated with atherosclerosis. Hypercholesterolemic patients with coronary artery disease (CAD) present increased plasmatic levels of C3 compared to healthy subjects or hypercholesterolemic patients without CAD [56]. Stimulation of human or rat hepatoma cells with the acute-phase inducer IL-6 increases the expression of the complement component C3 gene [57,58].…”

Proteomic Approach to the Study of Statin Pleiotropy in Kidney Transplant Patients

“…components C5a and C3 [40,41] . Moreover, serum levels of C4 have been suggested to monitor the anti-inflammatory effect of statins in patients with coronary artery disease [42] .…”