Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.

Increases in plasma LDL-cholesterol have unequivocally been established as a causal risk factor for atherosclerosis. Hence, strategies for lowering of LDL-cholesterol may have immediate therapeutic relevance. Here we study the role of human neutrophil peptide 1 (HNP1) in a mouse model of atherosclerosis and identify its potent atheroprotective effect both upon transgenic overexpression and therapeutic delivery. The effect was found to be due to a reduction of plasma LDL-cholesterol. Mechanistically, HNP1 binds to apolipoproteins enriched in LDL. This interaction facilitates clearance of LDL particles in the liver via LDL receptor. Thus, we here identify a non-redundant mechanism by which HNP1 allows for reduction of LDL-cholesterol, a process that may be therapeutically instructed to lower cardiovascular risk.

The results of investigations in 6 psoriasis patients, who have been treated with corticosteroid ointments (15–50 g daily) under occlusive dressings over a long period (minimum of 2 till more than 5 years) on the consequences of this therapy for the pituitary-adrenocortical system are related. In accordance with the literature a systemic effect during therapy is evident by a lowering of the 17-ketogenic steroids in the 24-hour urine and the plasma cortisol levels, and in an insufficient reaction to metyrapone. Stimulation with exogenous ACTH was followed by a normal adrenocortical response in all patients. With the insulin-tolerance test a good reaction to stress during therapy is found in the 5 tested patients. It is plausible, therefore, that the feedback system will resume its responsiveness after discontinuing the local therapy and that the suppression does not indicate permanent damage to the pituitary adrenal functions.

Hydrocortisone butyrate, when used topically in large quantities, can lead to suppression of the pituitary-adrenal system. This systemic effect apparently does not reduce pituitary-adrenal responsiveness.