Abstract
SummaryBackgroundHigh-density lipoproteins (HDL) have athero-protective biological properties: antioxidative, anti-apoptotic, anti-inflammatory, and they have the efflux capacity of cellular cholesterol. Plasma mRNA analysis can be used to investigate statin pleiotropy in vivo as a new analytical tool for non-invasive assessment of gene expression in vascular beds. The aim of this study was to assess the pleiotropic effects of atorvastatin in stable angina patients with high-risk values (group A) as compared with patients who had borderline and desirable HDL-cholesterol (HDL-C) values (group B).MethodsThe atorvastatin therapy (20 mg/day) was given to forty-three patients with stable angina for 10 weeks. We investigated three statin pleiotropy-targeted genes: inter-cellular adhesion molecule-1, chemokine (C-C motif) ligand 2 and cathepsin S and assessed by gel electrophoresis gradient the effects of atorvastatin on HDL size and subclasses.ResultsIn group A, after therapy, HDL-C concentration was significantly increased but not in group B. Atorvastatin lowered plasma chemokine (C-C motif) ligand 2 and intercellular adhesion molecule-1 mRNA levels in both groups, but did not change the plasma cathepsin S mRNA levels. In group A only, baseline total bilirubin showed negative correlations with the genes of cathepsin S (r=−0.506; p=0.023) and significantly increased after therapy.ConclusionsHDL-C and bilirubin can be promising therapeutic targets in the treatment of cardiovascular diseases. Analysis of cell-free mRNA in plasma might become a useful tool for estimating statin pleiotropy.
Highlights
High-density lipoproteins (HDL) have atheroprotective biological properties: antioxidative, antiapoptotic, antiinflammatory, and they have the efflux capacity of cellular cholesterol [1]
The literature is indicative of HDL-C antioxidative, antiapoptotic and antiinflammatory activities, in the study there were no correlations of HDL-C with bilirubin and HDL-C with genes that are significant for the aforementioned effects
This study indicates that atorvastatin in stable angina patients lowered the plasma messenger ribonucleic acid (mRNA) levels of statin pleiotropy-targeted genes intercellular adhesion molecule-1 (ICAM1) and gene encoding monocyte chemoattractant protein-1 (CCL2) in both groups
Summary
High-density lipoproteins (HDL) have atheroprotective biological properties: antioxidative, antiapoptotic, antiinflammatory, and they have the efflux capacity of cellular cholesterol [1]. These plasma HDL particles have heterogeneous physicochemical properties, metabolism, and biological activity [1]. Prospective studies have shown that coronary heart disease (CHD) risk was increased by 3% in women and by 2% in men per decrement of 1 mmol/L in HDL-C [3]. Common cardiovascular prevention strategies emphasise therapeutic reductions in low-density lipoprotein cholesterol (LDL-C) [4], attention is being focused on HDL cholesterol as a secondary prevention target to address the risk of residual cardiovascular disease (CVD) [5]
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