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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Modulation of Adhesion Molecules by Cholesterol-Lowering Therapy in Mononuclear Cells from Hypercholesterolemic Patients

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Author(s):
Cerda, Alvaro [1, 2] ; Rodrigues, Alice Cristina [3] ; Alves, Camila [1] ; Genvigir, Fabiana Dalla Vecchia [1] ; Fajardo, Cristina Moreno [1] ; Dorea, Egidio Lima [4] ; Gusukuma, Maria Cecilia [4] ; Pinto, Gelba Almeida [4] ; Hirata, Mario Hiroyuki [1] ; Crespo Hirata, Rosario Dominguez [1]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Analyses, BR-05508900 Sao Paulo, SP - Brazil
[2] Univ La Frontera, Ctr Mol Biol & Pharmacogenet, BIOREN CEGIN, Temuco - Chile
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Univ Hosp, BR-05508900 Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Cardiovascular Therapeutics; v. 33, n. 4, p. 168-176, AUG 2015.
Web of Science Citations: 7
Abstract

Introduction: Cholesterol-lowering therapy has been related with several pleiotropic effects including anti-inflammatory action in vascular endothelium; however, their influence on monocyte adhesion molecules is poorly described. Aims: To investigate the effect of inhibitors of synthesis (statins) and absorption (ezetimibe) of cholesterol on expression of adhesion molecules L-selectin, PSGL-1, VLA-4, LFA-1, and Mac-1 in mononuclear cells in vivo and in vitro using THP-1 cells. Methods: The influence of simvastatin (10 mg/day), ezetimibe (10 mg/day), and their combination (10 mg each/day) on mRNA expression of adhesion molecules was analyzed in peripheral blood mononuclear cells (PBMC) from hypercholesterolemics. The effects of atorvastatin, simvastatin, and ezetimibe on mRNA and protein expression of adhesion molecules were also evaluated in THP-1 cells. Results: Simvastatin/ezetimibe combination, but not the monotherapies, reduced the mRNA expression of the PSGL-1, LFA-1, and Mac-1 genes in PBMC from hypercholesterolemics. Total and LDL cholesterol in serum correlated with PSGL-1 mRNA expression, whereas HDL cholesterol negatively correlated with mRNA levels of L-selectin and VLA-4 genes (P < 0.05). Plasma hsCRP was also correlated with mRNA levels of VLA-4, LFA-1, and Mac-1 (P < 0.05). Atorvastatin and simvastatin at 10 mu M reduced mRNA and protein expression of L-selectin, PSGL-1, and VLA-4 in THP-1 cells (P < 0.05). Conclusion: Cholesterol-lowering therapy modulates gene expression of adhesion molecules in PBMC from hypercholesterolemics and THP-1 cells. Simvastatin/ezetimibe combination gives more benefits by reducing to a larger extent the expression of adhesion molecules in mononuclear cells. (AU)

FAPESP's process: 10/15353-8 - Role of statins on modulation of inflammation and cellular adhesion biomarkers in vivo and in vitro
Grantee:Rosario Dominguez Crespo Hirata
Support Opportunities: Regular Research Grants