Atherosclerosis is characterized by thickening of the walls of the arteries, a process that occurs slowly and 'silently' over decades. This prolonged course of disease provides a window of opportunity for diagnosis before symptoms occur. But, until recently, only advanced atherosclerotic disease could be observed. Now, developments in imaging technology offer many enticing prospects, including detecting atherosclerosis early, grouping individuals by the probability that they will develop symptoms of atherosclerosis, assessing the results of treatment and improving the current understanding of the biology of atherosclerosis.
It is assumed that the survival factors Bcl-2 and Bcl-xL are mainly functional on mitochondria and therefore must contain mitochondrial targeting sequences. Here we show, however, that only Bcl-xL is specifically targeted to the mitochondrial outer membrane (MOM) whereas Bcl-2 distributes on several intracellular membranes. Mitochondrial targeting of Bcl-xL requires the COOH-terminal transmembrane (TM) domain flanked at both ends by at least two basic amino acids. This sequence is a bona fide targeting signal for the MOM as it confers specific mitochondrial localization to soluble EGFP. The signal is present in numerous proteins known to be directed to the MOM. Bcl-2 lacks the signal and therefore localizes to several intracellular membranes. The COOH-terminal region of Bcl-2 can be converted into a targeting signal for the MOM by increasing the basicity surrounding its TM. These data define a new targeting sequence for the MOM and propose that Bcl-2 acts on several intracellular membranes whereas Bcl-xL specifically functions on the MOM.
Pulmonary artery stiffness increases early in the course of PH (even when PH is detectable only with exercise and before overt pressure elevations occur at rest). These observations suggest a potential contributory role of PA stiffness in the development and progression of PH.
Right ventriculo-arterial coupling in pulmonary hypertension can be studied with standard RHC and CMR. Arterial load increases with disease severity whereas contractility cannot progress in parallel, leading to severe uncoupling.
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