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The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein
Bosa Mirjanić-Azarić1, Zorana Jelić-Ivanović2, Aleksandra Zeljković2
1Department of Laboratory Diagnostics, Clinical Centre Banja Luka, Bosnia and Herzegovina; Faculty of Pharmacy, University of Ljubljana, Slovenia.
Insights
Atorvastatin therapy increased high-density lipoprotein cholesterol (HDL-C) and reduced specific inflammatory markers in stable angina patients. Plasma mRNA analysis shows potential for assessing statin pleiotropy and cardiovascular disease treatment targets.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Molecular Biology
Background:
- High-density lipoproteins (HDL) possess athero-protective properties including antioxidant, anti-apoptotic, and anti-inflammatory effects, alongside cholesterol efflux capacity.
- Plasma mRNA analysis offers a novel, non-invasive method to assess in vivo gene expression in vascular beds, aiding the study of statin pleiotropy.
- This study investigated the pleiotropic effects of atorvastatin in stable angina patients stratified by HDL-cholesterol (HDL-C) levels.
Purpose of the Study:
- To evaluate the pleiotropic effects of atorvastatin in patients with stable angina.
- To compare these effects between patients with high-risk HDL-C levels (Group A) and those with borderline/desirable HDL-C levels (Group B).
Main Methods:
- Forty-three stable angina patients received atorvastatin (20 mg/day) for 10 weeks.
- Investigated mRNA levels of intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2, and cathepsin S.
- Assessed atorvastatin's effect on HDL size and subclasses using gel electrophoresis gradient.
Main Results:
- Atorvastatin significantly increased HDL-C in Group A but not in Group B.
- Plasma mRNA levels of chemokine (C-C motif) ligand 2 and intercellular adhesion molecule-1 were reduced in both groups.
- Cathepsin S mRNA levels remained unchanged; however, in Group A, baseline total bilirubin negatively correlated with cathepsin S and increased post-therapy.
Conclusions:
- HDL-C and bilirubin show potential as therapeutic targets for cardiovascular diseases.
- Plasma cell-free mRNA analysis may serve as a valuable tool for evaluating statin pleiotropy.
- Atorvastatin demonstrates pleiotropic effects beyond lipid-lowering in stable angina patients.
Background:
High-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).
Methods:
The 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.
Results:
In 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.
Conclusions:
HDL-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.