Volume 217 | Issue 2 | August 2011

Highlighted Articles By Sarah Leigh (Editorial Assistant) and Steve Humphries (Editor–in-Chief)

Two articles examining leptin are published in this issue of Atherosclerosis. In their paper Singh et al show that leptin increases caveolin-1 expression, which in turn impairs leptin signalling in vascular endothelial cells and may contribute to the development of atherosclerosis. Furthermore, they propose a novel leptin feedback mechanism which may be involved in development of peripheral endothelium leptin resistance in obesity. In a clinical study Ku et al report that low leptin is associated with increased CV events and mortality in patients with stable coronary artery disease. They also reported that this relationship is modified by BMI, which may be explained by increased leptin resistance in obesity. The invited commentary by Devaraj & Torok puts both these studies into context and observes that while these studies give interesting insights into the multiple roles that leptin has in human health, much work is still needed to elucidate the mechanisms involved. Indeed Ku et al conclude that understanding the effects of leptin in the CV system may provide insight into the relationship between obesity and heart disease.

In view of the many studies that report an association between sleep duration and total mortality, Abe et al set out to assess atherosclerosis relative to sleep duration. Interestingly they found that long sleep duration (≥7h) correlated significantly with the incidence of carotid artery atherosclerosis compared with a sleep duration of 6h, but shorter sleep duration did not. In their invited commentary Grandner & Youngstedt commend Abe et al’s work as it is one of the first to make an assessment of sleep duration and atherosclerosis. Grandner & Youngstedt go on to discuss wider aspects of this field and suggest that, in the future, targeted strategies may be developed to improve sleep quality and quantity, and consequently health and longevity of the population.
 

Imaging papers

Impact of wall thickness on conduit artery function in humans: Is there a “Folkow” effect? Thijssen et al Using high resolution ultrasound and dilatation the authors have demonstrated for the first time that regional heterogeneity exists in the wall-to-lumen ratio within and between limbs. This difference in the architecture of healthy arteries has implications for their function and responsiveness to vasoactive stimuli, and therefore is broadly supporting Folkow’s hypothesis of the 1950s.
Imaging mass spectrometry-based histopathologic examination of atherosclerotic lesions Zaima et al Using imaging mass spectrometry based histopathologic examination, the authors have been able to reveal the characteristic peaks of lipid rich regions, SMCs, and calcified regions in atherosclerotic lesions, indicating that this approach is of considerable value as a new histopathologic examination. 

Review Articles

Mechanisms regulating hepatic SR-BI expression and their impact on HDL metabolism Leiva et al The evidence put forward in this review shows that an understanding of the critical steps involved in the regulation SR-BI gene expression as well as SR-BI synthesis, sorting, trafficking, turnover, recycling, degradation and protein–protein interaction in the liver may provide valuable insights into new alternatives for therapy in a variety of disease conditions associated with altered cholesterol metabolism.

Where does the interplay between cholesterol absorption and synthesis in the context of statin and/or ezetimibe treatment stand today? Descamps et al Using a literature search, the authors assessed studies that explored the influence of cholesterol absorption and synthesis, before or during hypolipemic treatment with statin and ezetimibe. They concluded that, with the exception of a reverse effect of statin and ezetimibe on absorption and synthesis, most ideas supporting the interplay between cholesterol absorption and synthesis lacked consistency between studies. At present, the use of the plasma levels of plant sterols and cholesterol precursors as markers of cholesterol absorption and synthesis is far too limited to definitively solve these questions.

Papers in this issue include:

Vascular Biology, Hemostasis & Oxidative Stress

• miR-146a is Modulated in Human Endothelial Cell with Aging.
• Targeting Therapeutics to the Vascular Wall in Atherosclerosis - Carrier Size Matters.

Metabolism: Lipids, Lipoproteins, Carbohydrates, Homocysteine & Cholesterol

• Apolipoprotein A-I Mimetic Peptide, ETC-642 exhibits Anti-Inflammatory Properties that are Comparable to High-Density Lipoproteins.
• HMG-CoA reductase inhibitors enhance phagocytosis by upregulating ATP-binding cassette transporter A7.

Imaging and Measurement of Vessel Health

• Impact of wall thickness on conduit artery function in humans: is there a “Folkow Effect?”.
• Relationships of night/day heart rate ratio with carotid IMT & markers of arterial stiffness. 

Genetics

• Meta analysis of candidate gene variants outside the LPA locus with Lp(a) plasma levels in 14,500 participants of six White European cohorts.
• A SNP in exon 3 of the kallikrein 1 gene: associated with large but not small AAA.

Intervention

• Plant stanol esters lower LDL cholesterol level in statin-treated subjects with type 1 diabetes by interfering the absorption & synthesis of cholesterol.
• Cost-effectiveness of enhancing adherence to therapy with statins in the setting of primary cardiovascular prevention. Evidence from an empirical approach based on administrative databases.

Epidemiology, Biomarkers and Nutrition

• Leptin upregulates caveolin-1 expression: Implications for development of atherosclerosis.
• Association of low leptin with cardiovascular events and mortality in patients with stable coronary artery disease: The Heart and Soul Study.
• Sleep duration is significantly associated with carotid artery atherosclerosis incidence in a Japanese population.