Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase inhibitors reduces the incidence of atherosclerosis-related cardiovascular events. Adhesion molecules, regulating interactions between vascular and circulating cells, may play a central role in the pathogenesis of atherosclerosis and related complications. In the present report we examined the impact of the HMG-CoA reductase inhibitor fluvastatin on plasma levels of P-selectin and ICAM-1.
Methods
Plasma levels of P-selectin and ICAM-1 were determined using an enzyme immunoassay in 26 patients with type IIa hypercholesterolemia randomized to treatment with either fluvastatin (80 mg/d) or placebo in a double blind fashion for 12 weeks.
Results
Fluvastatin administration reduced either P-selectin (118±63 vs 81±36 ng/mL [-31%], P=0.0015) or ICAM-1 (264±75 vs 228±68 ng/mL [-13.7%), P=0.0033) levels. Fluvastatin also lowered urinary 11-dehydro-TXB2 (1396±536 vs 1009±378 pg/mg creatinine [-27%], P=0.0015) and von Willebrand Factor levels (1456±716 vs 1203±527 U/L [-17.4%], P=0.0275), and a direct correlation was observed between P-selectin and 11-dehydro-TXB2 levels (r=0.588, P=0.0033). Patients treated with fluvastatin displayed an increase in nitric oxide (NO) generation, evaluated with measurements of serum NO2-/NO3, (4.7±1 vs 8.9±3.1 µmol/L [98%], P=0.0046). Moreover, an inverse correlation was observed between NO2/NO3 and P-selectin (r=-0.420; P=0.0343), 11-dehydro-TXB2 (r=-0.511; P=0.0106), or LDL (r=-0.742; P=0.0002) levels.
Conclusions
These results may provide novel biochemical basis for the beneficial clinical effects of HMG-CoA reductase inhibitors in hypercholesterolemia.
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