Flow-Dependent Remodeling of Small Arteries in Mice Deficient for Tissue-Type Transglutaminase

Chronic changes in blood flow induce an adaptation of vascular caliber. Thus, arteries show inward remodeling after a reduction in blood flow. We hypothesized that this remodeling depends on the crosslinking enzyme tissue-type transglutaminase (tTG). Flow-dependent remodeling was studied in wild-type (WT) and tTG-null mice using a surgically imposed change in blood flow in small mesenteric arteries. WT mice showed inward remodeling after 2 days of low blood flow, which was absent in arteries from tTG-null mice. Yet, after continued low blood flow for 7 days, inward remodeling was similar in arteries from WT and tTG-null mice. Studying the alternative pathways of remodeling, we identified a relatively high expression of the plasma transglutaminase factor XIII in arteries of WT and tTG-null mice. In addition, vessels from both WT and tTG-null mice showed the presence of transglutaminase-specific crosslinks. An accumulation of adventitial monocytes/macrophages was found in vessels exposed to low blood flow in tTG-null mice. Because monocytes/macrophages may represent a source of factor XIII, tTG-null mice were treated with liposome-encapsulated clodronate. Elimination of monocytes/macrophages with liposome-encapsulated clodronate reduced both the expression of factor XIII and inward remodeling in tTG-null mice. In conclusion, tTG plays an important role in the inward remodeling of small arteries associated with decreased blood flow. Adventitial monocytes/macrophages are a source of factor XIII in tTG-null mice and contribute to an alternative, delayed mechanism of inward remodeling when tTG is absent

Modelling Parameter Role on Accuracy of Cardiac Perfusion Quantification

\u3cp\u3eCardiovascular magnetic resonance (CMR) perfusion data are suitable for quantitative measurement of myocardial blood flow. The goal of perfusion-CMR post- processing is to recover tissue impulse-response from observed signal-intensity curves. While several deconvolution techniques are available for this purpose, all of them use models with varying parameters for the representation of the impulse-response. However this variation influences the accuracy of the deconvolution and introduces possible variations in the results. Using an appropriate order for quantification is essential to allow CMR-perfusion-quantification to develop into a useful clinical tool. The aim of this study was to evaluate the effect of parameter variation in Fermi modelling, autoregressive moving-average model (ARMA), B-spline-basis and exponential-basis deconvolution. Whilst Fermi is the least dependent method on the modelling parameter determination, the B-spline and ARMA were the most sensitive models to this variation. ARMA upon a correct choice of order showed to be the superior to other methods.\u3c/p\u3