Endothelial Heparan Sulfate Proteoglycans in Sepsis: The Role of the Glycocalyx.

There is increasing recognition of the importance of the endothelial glycocalyx and its in vivo manifestation, the endothelial surface layer, in vascular homeostasis. Heparan sulfate proteoglycans (HSPGs) are a major structural constituent of the endothelial glycocalyx and serve to regulate vascular permeability, microcirculatory tone, leukocyte and platelet adhesion, and hemostasis. During sepsis, endothelial HSPGs are shed through the induction of "sheddases" such as heparanase and matrix metalloproteinases, leading to loss of glycocalyx integrity and consequent vascular dysfunction. Less well recognized is that glycocalyx degradation releases HSPG fragments into the circulation, which can shape the systemic consequences of sepsis. In this review, we will discuss (1) the normal, homeostatic functions of HSPGs within the endothelial glycocalyx, (2) the pathological changes in HSPGs during sepsis and their consequences on the local vascular bed, and (3) the systemic consequences of HSPG degradation. In doing so, we will identify potential therapeutic targets to improve vascular function during sepsis as well as highlight key areas of uncertainty that require further mechanistic investigation.

Increased intrathoracic and hepatic visceral adipose tissue independently correlates with coronary artery calcification in asymptomatic patients.

BACKGROUND: Visceral adipose tissue (VAT) is associated with cardiac events, but it is not clear which, if any of the various measures of VAT independently correlate with coronary artery disease (CAD). METHODS: We studied 400 patients undergoing computed tomography to determine coronary artery calcium (CAC) score. VAT was measured in the form of epicardial adipose tissue (EAT) volume and thickness, intrathoracic adipose tissue volume (ITAV), and hepatic steatosis. RESULTS: Of the 400 subjects, the average CAC score was 112.2 ± 389.3. When each measure of VAT (EAT volume and thickness, ITAV, hepatic steatosis) was added to the traditional model (they were independently associated with greater risk of CAC score ≥100 AU as measured by IDI/NRI (P < .05). On univariable logistic regression analysis, each of the 4 measures of VAT showed association with greater risk of a CAC score of ≥100 AU (OR > 1). CONCLUSIONS: Each measure of VAT is a strong correlate of CAC score ≥100 AU in asymptomatic subjects-these VAT assessments correlate more significantly than do traditional CAD risk factors. This incremental power in the predictive models is likely the result of measurement of a fundamental expression of the metabolic syndrome and consequent proatherogenic derangements.

Computed tomographic evidence of atherosclerosis in the mummified remains of humans from around the world.

Although atherosclerosis is widely thought to be a disease of modernity, computed tomographic evidence of atherosclerosis has been found in the bodies of a large number of mummies. This article reviews the findings of atherosclerotic calcifications in the remains of ancient people-humans who lived across a very wide span of human history and over most of the inhabited globe. These people had a wide range of diets and lifestyles and traditional modern risk factors do not thoroughly explain the presence and easy detectability of this disease. Nontraditional risk factors such as the inhalation of cooking fire smoke and chronic infection or inflammation might have been important atherogenic factors in ancient times. Study of the genetic and environmental risk factors for atherosclerosis in ancient people may offer insights into this common modern disease.