Rationale: S100A12 is a small calcium binding protein that is a ligand of RAGE (receptor for advanced glycation end products). RAGE has been extensively implicated in inflammatory states such as atherosclerosis, but the role of S100A12 as its ligand is less clear. Objective: To test the role of S100A12 in vascular inflammation, we generated and analyzed mice expressing human S100A12 in vascular smooth muscle under control of the smooth muscle 22␣ promoter because S100A12 is not present in mice. Methods and Results: Transgenic mice displayed pathological vascular remodeling with aberrant thickening of the aortic media, disarray of elastic fibers, and increased collagen deposition, together with increased latent matrix metalloproteinase-2 protein and reduction in smooth muscle stress fibers leading to a progressive dilatation of the aorta. In primary aortic smooth muscle cell cultures, we found that S100A12 mediates increased interleukin-6 production, activation of transforming growth factor ␤ pathways and increased metabolic activity with enhanced oxidative stress. To correlate our findings to human aortic aneurysmal disease, we examined S100A12 expression in aortic tissue from patients with thoracic aortic aneurysm and found increased S100A12 expression in vascular smooth muscle cells. Conclusions: S100A12 expression is sufficient to activate pathogenic pathways through the modulation of oxidative stress, inflammation and vascular remodeling in vivo. (Circ Res. 2010;106:145-154.)

Gastrointestinal stasis during sepsis may be associated with gastrointestinal smooth muscle dysfunction. Endotoxin [lipopolysaccharide (LPS)] impairs smooth muscle contraction, in part through inducible nitric oxide synthase (NOS II) and enhanced nitric oxide production. We studied the roles of tumor necrosis factor-α (TNF) and interleukin-1 (IL-1) in this process by using TNF binding protein (TNFbp) and IL-1 receptor antagonist (IL-1ra). Rats were treated with TNFbp and IL-1ra, or their vehicles, 1 h before receiving LPS or saline. At 5 h after LPS, contractility was measured in strips of ileal longitudinal smooth muscle, and NOS II activity was measured in full-thickness segments of ileum. LPS decreased maximum stress (mean ± SE) from 508 ± 55 (control) to 355 ± 33 g/cm2( P < 0.05). Pretreatment with TNFbp plus IL-1ra prevented the LPS-induced decrease. Separate studies of TNFbp alone or IL-1ra alone indicated that, at the doses and timing used, TNFbp was more effective. LPS also increased NOS II activity by >10-fold ( P < 0.01) over control. This increase was prevented by TNFbp plus IL-1ra ( P = not significant vs. control). We conclude that the LPS-induced increase in NOS II activity and the decrease in ileal muscle contractility are mediated by TNF and IL-1.

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RT3D TEE can be used to guide transcatheter ASD closure with the advantages of lower cost than ICE, and ability to visualize en-face views of the ASD. ASD and BD as measured by RT3D TEE differ when compared with 2D imaging.

RV/LV EDD ratio > 0.7 has good accuracy for the diagnosis of acute PE. RV/LV area ratio > 0.7 and McConnell sign are specific but not sensitive indicators of acute pulmonary embolism. The presence of these findings should prompt further diagnostic testing for PE.