OBJECTIVES: We sought to determine whether inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase with pravastatin affects transforming growth factor-beta(1) (TGF-beta(1)) circulating levels and its production in the monocytes of hypercholesterolemic patients. BACKGROUND: Transforming growth factor-beta(1) is a multifunctional growth factor/cytokine involved in many physiologic and pathologic processes, such as vascular remodeling and atherogenesis. Statins have been reported to have a modulatory role in cytokine expression in the monocytes of hyperlipidemic patients. METHODS: We evaluated, in a cross-over study design, plasma TGF-beta(1) levels and ex vivo TGF-beta(1) production in the monocytes of hypercholesterolemic patients before and after four to six weeks of lipid-lowering treatment with diet or diet plus 40 mg/day of pravastatin. In addition, isolated blood monocytes were subjected to pravastatin treatment and evaluated for TGF-beta(1) messenger ribonucleic acid (mRNA) expression and TGF-beta(1) in vitro production. RESULTS: Lipid-lowering treatment significantly decreased total cholesterol and low-density lipoprotein cholesterol plasma levels. Pravastatin, but not a low lipid diet, induced a significant increase in TGF-beta(1) plasma levels (from 1.7 +/- 0.5 ng/ml to 3.1 +/- 1.1 ng/ml, p < 0.001) and in ex vivo monocyte production (from 1.8 +/- 0.8 ng/ml to 3.9 +/- 1.0 ng/ml, p < 0.001). The increase in TGF-beta(1) levels was not related to the changes in the lipid profile observed with pravastatin. An increase of approximately twofold in TGF-beta(1) production and in mRNA expression was also observed after in vitro treatment of human monocytes with pravastatin (5 microM). Co-incubation with mevalonate reversed the in vitro effect of pravastatin. CONCLUSIONS:3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition with pravastatin increases TGF-beta(1) plasma levels, as well as monocyte production, in hypercholesterolemic patients. The mevalonate pathway plays a role in the regulation of TGF-beta(1) expression in human monocytes. A possible implication in the biologic and clinical effects of statins can be suggested.
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OBJECTIVES: We sought to determine whether inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase with pravastatin affects transforming growth factor-beta(1) (TGF-beta(1)) circulating levels and its production in the monocytes of hypercholesterolemicpatients. BACKGROUND:Transforming growth factor-beta(1) is a multifunctional growth factor/cytokine involved in many physiologic and pathologic processes, such as vascular remodeling and atherogenesis. Statins have been reported to have a modulatory role in cytokine expression in the monocytes of hyperlipidemic patients. METHODS: We evaluated, in a cross-over study design, plasma TGF-beta(1) levels and ex vivo TGF-beta(1) production in the monocytes of hypercholesterolemicpatients before and after four to six weeks of lipid-lowering treatment with diet or diet plus 40 mg/day of pravastatin. In addition, isolated blood monocytes were subjected to pravastatin treatment and evaluated for TGF-beta(1) messenger ribonucleic acid (mRNA) expression and TGF-beta(1) in vitro production. RESULTS:Lipid-lowering treatment significantly decreased total cholesterol and low-density lipoprotein cholesterol plasma levels. Pravastatin, but not a low lipid diet, induced a significant increase in TGF-beta(1) plasma levels (from 1.7 +/- 0.5 ng/ml to 3.1 +/- 1.1 ng/ml, p < 0.001) and in ex vivo monocyte production (from 1.8 +/- 0.8 ng/ml to 3.9 +/- 1.0 ng/ml, p < 0.001). The increase in TGF-beta(1) levels was not related to the changes in the lipid profile observed with pravastatin. An increase of approximately twofold in TGF-beta(1) production and in mRNA expression was also observed after in vitro treatment of human monocytes with pravastatin (5 microM). Co-incubation with mevalonate reversed the in vitro effect of pravastatin. CONCLUSIONS: 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition with pravastatin increases TGF-beta(1) plasma levels, as well as monocyte production, in hypercholesterolemicpatients. The mevalonate pathway plays a role in the regulation of TGF-beta(1) expression in human monocytes. A possible implication in the biologic and clinical effects of statins can be suggested.
Authors: Ana Lucía Rodríguez-Perea; Carlos J Montoya; Sven Olek; Claire A Chougnet; Paula A Velilla Journal: J Immunol Res Date: 2015-02-22 Impact factor: 4.818
Authors: Juan Rodríguez-Vita; Eva Sánchez-Galán; Beatriz Santamaría; Elsa Sánchez-López; Raquel Rodrigues-Díez; Luís Miguel Blanco-Colio; Jesús Egido; Alberto Ortiz; Marta Ruiz-Ortega Journal: PLoS One Date: 2008-12-17 Impact factor: 3.240