Atorvastatin treatment increases plasma bilirubin but not HMOX1 expression in stable angina patients. (September 2015)

• Record Type: Journal Article
• Authors: Mirjanic-Azaric, Bosa; Rizzo, Manfredi; Jürgens, Günther; Hallstroem, Seth; Srdic, Svetozar; Marc, Janja; Cerne, Darko
• Is Part Of: Scandinavian journal of clinical & laboratory investigation. Volume 75:Number 5(2015)
• Page Start: 382
• Page End: 389
• Publication Date: 2015-09
• Subjects: Clinical biochemistry -- Periodicals; Physiology, Pathological -- Periodicals; Physiology, Experimental -- Periodicals; Medicine -- Research -- Periodicals; Clinical medicine -- Periodicals; 616.0072
• DOI: 10.3109/00365513.2015.1031691
• Languages: English
• ISSNs: 0036-5513

Abstract

<abstract> <title>Abstract</title> <p> <bold> <italic>Background</italic>.</bold> <italic>In vitro</italic> and animal studies indicate that statins increase heme oxygenase-1 gene (<italic>HMOX1</italic>) expression, which then, presumably, increases plasma bilirubin concentration. However, clinical confirmation that statins concomitantly increase <italic>HMOX1</italic> expression and plasma bilirubin concentration is lacking. We hypothesized that in patients with stable angina atorvastatin therapy (20 mg/day for 10 weeks) concomitantly increases total bilirubin concentration and <italic>HMOX1</italic> expression, as assessed non-invasively by plasma analysis. <bold><italic>Methods</italic>.</bold> In 44 patients with stable angina plasma concentrations of total bilirubin, <italic>HMOX1</italic> mRNA and HMOX1 protein were measured before and after the statin treatment, as well as plasma concentrations of oxidized low-density lipoprotein (OxLDL), malondialdehyde (MDA), monocyte chemoattractant protein (MCP-1) and C-reactive protein (CRP). <bold><italic>Results</italic>.</bold> Atorvastatin treatment increased total bilirubin concentration (median 6.95 μmol/L vs. 8.55, + 23.02%; <italic>p</italic> < 0.001), but did not change plasma <italic>HMOX1</italic> mRNA and HMOX1 protein concentrations. Plasma concentrations of OxLDL (− 31.85%, <italic>p</italic> < 0.001), MCP-1 (− 16.20%, <italic>p</italic> = 0.020) and CRP (− 7.32%, <italic>p</italic> = 0.010) were decreased but MDA was not decreased (15.32%, <italic>p</italic> = 0.107). Within subjects, increment of plasma bilirubin concentration did not correlate with the changes in <italic>HMOX1</italic> mRNA and protein concentrations, but correlated with low-density lipoprotein cholesterol decrement (<italic>r</italic> = − 0.374, <italic>p</italic> = 0.012). Bilirubin increment did not correlate with the changes in oxidative and inflammatory markers. <bold><italic>Conclusion</italic>.</bold> Our prospective observational trial finally confirms that atorvastatin (20 mg/day for 10 weeks) increases plasma total bilirubin concentration. However, it seems that this effect is HMOX1-independent.</p> </abstract>