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J Investig Med. 2000 May;48(3):183-9.

Fluvastatin reduces soluble P-selectin and ICAM-1 levels in hypercholesterolemic patients: role of nitric oxide.

Author information

1
Institute of Medical Pathology and Mediterranean Medicine, University of Messina, Italy.

Abstract

BACKGROUND:

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) mumol/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.

PMID:
10822898
[Indexed for MEDLINE]

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