The Redox State of Transglutaminase 2 Controls Arterial Remodeling

While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates, and its specific mode of action during small artery inward remodeling. We found that inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required the presence of a reducing agent. The effect of TG2 depended on its cross-linking activity, as indicated by the lack of effect of mutant TG2. The cell-permeable reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced translocation of endogenous TG2 and high membrane-bound transglutaminase activity. This coincided with inward remodeling, characterized by a stiffening of the artery. The remodeling could be inhibited by a TG2 inhibitor and by the nitric oxide donor, SNAP. Using a pull-down assay and mass spectrometry, 21 proteins were identified as TG2 cross-linking substrates, including fibronectin, collagen and nidogen. Inward remodeling induced by low blood flow was associated with the upregulation of several anti-oxidant proteins, notably glutathione-S-transferase, and selenoprotein P. In conclusion, these results show that a reduced state induces smooth muscle membrane-bound TG2 activity. Inward remodeling results from the cross-linking of vicinal matrix proteins, causing a stiffening of the arterial wall

Short-term effects of crisis response planning on optimism in a U.S. Army sample

Aim: This study examined the short-term effects of a brief crisis intervention on optimism of acutely suicidal soldiers. Methods: U.S. Soldiers (N = 97) presenting for an emergency mental health appointment in a military emergency department or behavioural health clinic were randomly assigned to treatment as usual standard crisis response plan, or enhanced crisis response plan (E-CRP). This study is used a subsample of the original clinical trial (n = 64) for those who completed self-report measures of optimism (Life Orientation Test-Revised) prior to receiving any intervention and a secondary self-report assessment one-month following the intervention. Results: Results indicate that individuals with low baseline optimism who received the E-CRP had significant increases in optimism 1 month post-intervention. Conclusion: This provides evidence that discussing a patient's reasons for living during a CRP increases optimism in those high-risk patients with the lowest baseline optimism. © 2018 John Wiley & Sons Australia, Lt