Atherosclerotic Plaque Vulnerability in Experimental Models of Atherosclerosis

Atherosclerosis is a chronic and often progressive disease of the wall of the arterial vasculature. The term atherosclerosis is derived from the Greek words “athero” meaning gruel or paste and “skleros” meaning stiff or hard. Atherosclerosis is considered a major clinical problem, which underlies most ischemic events of both the heart as well as the brain. It is the result of the Western lifestyle and can start very early in life even in persons without a strong genetic disposition like untreated familial hypercholesteremia. From the second decade onwards, the disease progresses more rapidly. The clinical silence of atherosclerosis is often broken between the 3rd and 5th decade, when patients present with ischemic complaints of e.g. heart and brain. Despite the continuing decrease in cardiovascular disease (CVD) associated death over the last decade, it still is one of the main causes of death in The Netherlands, accounting for 30,7% of total deaths in 2007. As a result, the socio-economic consequences remain huge. It has been estimated that in the European Union annual CVD-associated costs are €169 billion, of which €105 billion are costs directly related to healthcare. Historically, atherosclerosis was simply considered as an accumulation of lipids in the vascular wall. In the

Fibromodulin Deficiency Reduces Low-Density Lipoprotein Accumulation in Atherosclerotic Plaques in Apolipoprotein E-Null Mice.

OBJECTIVE: The aim of this study was to analyze how an altered collagen structure affects development of atherosclerotic plaques. METHODS AND RESULTS: Fibromodulin-null mice develop an abnormal collagen fibril structure. In apolipoprotein E (ApoE)-null and ApoE/fibromodulin-null mice, a shear stress-modifying carotid artery cast induced formation of atherosclerotic plaques of different phenotypes; inflammatory in low-shear stress regions and fibrous in oscillatory shear stress regions. Electron microscopy showed that collagen fibrils were thicker and more heterogeneous in oscillatory shear stress lesions from ApoE/fibromodulin-null mice. Low-shear stress lesions were smaller in ApoE/fibromodulin-null mice and contained less lipids. Total plaque burden in aortas stained en face with Oil Red O, as well as lipid accumulation in aortic root lesions, was also decreased in ApoE/fibromodulin-null mice. In addition, lipid accumulation in RAW264.7 macrophages cultured on fibromodulin-deficient extracellular matrix was decreased, whereas levels of interleukin-6 and -10 were increased. Our results show that an abnormal plaque collagen fibril structure can influence atherosclerotic plaque development. CONCLUSIONS: The present findings suggest a more complex role for collagen in plaque stability than previously anticipated, in that it may promote lipid-accumulation and inflammation at the same time as it provides mechanical stability

[DRESS syndrome as a result of sulfasalazine use].

A 24-year-old female developed DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) as a result of sulfasalazine use. The DRESS syndrome is a severe and acute hypersensitivity reaction that can be caused by a variety of drugs. The clinical presentation is diverse; the most common symptoms are fever, exanthema and lymphadenopathy. Haematologic abnormalities such as leukocytosis, accompanied primarily with eosinophilia, and sometimes atypical lymphocytes are also frequently reported. In most cases the DRESS syndrome needs no further treatment after discontinuation of the associated drug. However, 20% of patients are severely affected and the DRESS syndrome is potentially life-threatening. The patient was successfully treated with a glucocorticoid and an antihistamine

Supraventricular arrhythmia in pregnancy

The physiological changes during pregnancy predispose a woman for the development of new-onset or recurrent arrhythmia. Supraventricular arrhythmia is the most common form of arrhythmia during pregnancy and, although often benign in nature, can be concerning. We describe three complex cases of supraventricular arrhythmia during pregnancy and review the currently available literature on the subject. In pregnancies complicated by arrhythmia, a plan for follow-up and both maternal and fetal monitoring during pregnancy, delivery and post partum should be made in a multidisciplinary team. Diagnostic modalities should be used as in non-pregnant women if there is an indication. All antiarrhythmic drugs cross the placenta, but when necessary, medical treatment should be used with consideration to the fetus and the mother's altered pharmacodynamics and kinetics. Electrical cardioversion is safe during pregnancy, and electrophysiological study and catheter ablation can be performed in selected patients, preferably with zero-fluoroscopy technique. Sometimes, delivering the fetus (if viable) is the best therapeutic option. In this review, we provide a framework for the workup and clinical management of supraventricular arrhythmias in pregnant women, including cardiac, obstetric and neonatal perspectives