Identification of membrane palmitoylated protein 1 (MPP1) as a heart-failure-promoting protein triggered by cardiovascular risk factors and aging.

Membrane-Associated Guanylate Kinase (MAGUK) proteins are scaffold proteins with well-established functions in the neuronal system. A role of MAGUK protein up-regulation in the pathogenesis of heart failure is not established. This study identified the up-regulation of the MAGUK family protein MPP1 (Membrane Palmitoylated Protein 1), in cardiac transcriptome data of three different heart failure models. MPP1 was up-regulated in failing hearts of B6 mice with long-term chronic pressure overload, in failing hearts of aged Apoe-/- mice with long-term atherosclerosis, and in failing hearts of RKIP-transgenic mice with cardiotoxic lipid overload. MPP1-transgenic mice revealed that moderately (2-fold) increased cardiac MPP1 levels caused symptoms of heart failure with a significantly reduced left ventricular ejection fraction of 39.0 ± 6.9 % in Tg-MPP1 mice compared to 55.2 ± 3.7 % of non-transgenic B6 controls. Echocardiographic and histological analyses detected cardiac enlargement and cardiac dilation in Tg-MPP1 mice. The angiotensin II AT1 receptor (AGTR1) and MPP1 were co-localized on sarcolemmal membranes in vivo, and Tg-MPP1 mice had increased levels of cardiac AGTR1, which has an established heart failure-promoting function. The increased AGTR1 protein could be directly triggered by elevated MPP1 because MPP1 also increased the AGTR1 protein in non-cardiomyocyte HEK cells, which was detected by fluorescence measurement of AGTR1eYFP. MPP1 was not only up-regulated by major cardiovascular risk factors but also by old age, which is a major contributor to heart failure. Thus, the aging-induced MPP1 exerts a previously unrecognized role in heart failure pathogenesis by upregulation of the angiotensin II AT1 receptor (AGTR1) protein.

Traffic accident or dumping? - Striking results of a traffic accident reconstruction.

An atypical traffic accident scenario should be investigated directly at the crash site from all concerned professions, especially police men, forensic pathologists and technical experts, to get a personal overview and impression of the situation and the opportunity for interdisciplinary discussion. We present the rare case of a fatal traffic accident on a German motorway which was initially thought to be an accidental discovery of dumping a corpse. Based on autopsy findings, the technical investigation and the accident reconstruction, this case was solved as a spectacular form of a collision between a pedestrian and a bonnet-front car, which was not described elsewhere in scientific literature to the best of our knowledge. The pedestrian was hit in an upright body position, was lifted up by the car, smashed the windscreen and flew over the car with several body rotations. His flight curve ends directly at the roof of the car during brake processing, where the body touched the roof, smashed the rear-window and landed in the trunk. Based on the technical investigation, the driver of the car was not able to hide the accident. However, the pedestrian could have avoided the collision if he did not cross the motorway on foot.