Highlighted Articles - Atherosclerosis October 2015 Issue
23 October 2015
Volume 242 Issue 2 October 2015
By Elvira Mambetisaeva, Sarah Leigh and Steve Humphries (Editor–in-Chief)
Turner et al set out to understand the role of TGFβ signalling components in the regulation of COL4A1 and COL4A2 expression and to see if such components interact directly with the COL4A1 and COL4A2 loci previously associated with coronary artery disease (CAD). From their experiments they were able to conclude that TGFβ1 stimulates expression of the COL4A1 and COL4A2 genes via SMAD3/ SMAD4 in human aortic smooth muscle cells. Bearing in mind that their results suggested that activation of COL4A1/COL4A2 by SMAD3/SMAD4 may not be direct, they went on to perform meta-analysis of five CAD case control cohorts (4956 cases & 2774 controls). This study revealed significant gene -gene interaction, i.e.: epistasis. In his invited commentary, Aldons Lusis praises this important study for its analysis of a complex pathway in CAD, thereby revealing potential targets for further investigation and clinical intervention. He goes on to remark that the role of epistatic interactions in CAD may reveal further mechanistic information and also help in the understanding of the complex inheritance patterns of this condition.
In an attempt to establish whether or not low high density lipoprotein cholesterol (HDL-C) levels are a risk factor for CAD, Izuhara et al retrospectively evaluated 10391 CAD patients undergoing percutaneous coronary intervention during 2005-2007. Their main finding indicated that low HDL-C was not associated with a higher 5-year risk of major adverse cardiac events. Carlos Santos-Gallego in his invited commentary points out that Izuhara et al should be commended for the large sample size in their study and for the use of ‘rigorous and solid methodology’. This study strengthens the view that HDL function / quality are more relevant than HDL-C quantity and its evaluation would be a better predictor of future CAD risk than the quantity of HDL-C.
Kataoka et al reported the results of a retrospective cross-sectional study in which they performed optical coherence tomography (OCT) in non-obstructed vessels of 280 patients with stable angina who had undergone intensive low density lipoprotein cholesterol (LDL-C) lowering therapy. The results showed that LDL-C level and high dose statin use were independently associated with fibrous cap thickness. Ahn et al observe in their invited commentary that in this study the cross-sectional nature does not allow a causative relationship to be established. To address this issue they recommend that additional inflammatory and oxidative stress biomarker data might have been able to inform the interaction between LDL-C, cap thickness and relevant atherosclerotic pathways.
The review by Matthew Ito evaluates the literature to assess the therapeutic options for the treatment of hypertriglyceridemia, focussing on fibrates, niacin or long-chain omega-3 fatty acids (OM3FAs). He discusses their effectiveness and the drug-drug interactions associated with these agents, and concludes that OM3FAs and fibrates appear to be well tolerated and effective treatments for hypertriglyceridemia.
Papers in this issue include: