MMP-2 Isoforms in Aortic Tissue and Serum of Patients with Ascending Aortic Aneurysms and Aortic Root Aneurysms

ObjectiveThe need for biological markers of aortic wall stress and risk of rupture or dissection of ascending aortic aneurysms is obvious. To date, wall stress cannot be related to a certain biological marker. We analyzed aortic tissue and serum for the presence of different MMP-2 isoforms to find a connection between serum and tissue MMP-2 and to evaluate the potential of different MMP-2 isoforms as markers of high wall stress.MethodsSerum and aortic tissue from n = 24 patients and serum from n = 19 healthy controls was analyzed by ELISA and gelatin zymography. 24 patients had ascending aortic aneurysms, 10 of them also had aortic root aneurysms. Three patients had normally functioning valves, 12 had regurgitation alone, eight had regurgitation and stenosis and one had only stenosis. Patients had bicuspid and tricuspid aortic valves (9/15). Serum samples were taken preoperatively, and the aortic wall specimen collected during surgical aortic repair.ResultsPro-MMP-2 was identified in all serum and tissue samples. Pro-MMP-2 was detected in all tissue and serum samples from patients with ascending aortic/aortic root aneurysms, irrespective of valve morphology or other clinical parameters and in serum from healthy controls. We also identified active MMP-2 in all tissue samples from patients with ascending aortic/aortic root aneurysms. None of the analyzed serum samples revealed signals relatable to active MMP-2. No correlation between aortic tissue total MMP-2 or tissue pro-MMP-2 or tissue active MMP-2 and serum MMP-2 was found and tissue MMP-2/pro-MMP-2/active MMP-2 did not correlate with aortic diameter. This evidence shows that pro-MMP-2 is the predominant MMP-2 species in serum of patients and healthy individuals and in aneurysmatic aortic tissue, irrespective of aortic valve configuration. Active MMP-2 species are either not released into systemic circulation or not detectable in serum. There is no reliable connection between aortic tissue—and serum MMP-2 isoforms, nor any indication that pro-MMP-2 functions as a common marker of high aortic wall stress.     

Communal range defence in primates as a public goods dilemma

Classic socio-ecological theory holds that the occurrence of aggressive range defence is primarily driven by ecological incentives, most notably by the economic defendability of an area or the resources it contains. While this ecological cost–benefit framework has great explanatory power in solitary or pair-living species, comparative work on group-living primates has always found economic defendability to be a necessary, but not sufficient condition to account for the distribution of effective range defence across the taxon. This mismatch between theory and observation has recently been ascribed to a collective action problem among group members in, what is more informatively viewed as, a public goods dilemma: mounting effective defence of a communal range against intrusions by outgroup conspecifics. We here further develop this framework, and report on analyses at three levels of biological organization: across species, across populations within a single lineage and across groups and individuals within a single population. We find that communal range defence in primates very rarely involves collective action sensu stricto and that it is best interpreted as the outcome of opportunistic and strategic individual-level decisions. Whether the public good of a defended communal range is produced by solitary, joint or collective action is thus the outcome of the interplay between the unique characteristics of each individual, local and current socio-ecological conditions, and fundamental life-history traits of the species.     

A photoswitchable GPCR-based opsin for presynaptic inhibition

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Synthesis and SAR of 4-aminocyclopentapyrrolidines as orally active N-type calcium channel inhibitors for inflammatory and neuropathic pain

A novel series of N-type calcium channel inhibitors have been discovered. Optimization of potency and HT-ADME properties provides 4-aminocyclopentapyrrolidines with analgesic efficacy after oral dosing.