Pulsatile shear and Gja5 modulate arterial identity and remodeling events during flow-driven arteriogenesis

In the developing chicken embryo yolk sac vasculature, the expression of arterial identity genes requires arterial hemodynamic conditions. We hypothesize that arterial flow must provide a unique signal that is relevant for supporting arterial identity gene expression and is absent in veins. We analyzed factors related to flow, pressure and oxygenation in the chicken embryo vitelline vasculature in vivo. The best discrimination between arteries and veins was obtained by calculating the maximal pulsatile increase in shear rate relative to the time-averaged shear rate in the same vessel: the relative pulse slope index (RPSI). RPSI was significantly higher in arteries than veins. Arterial endothelial cells exposed to pulsatile shear in vitro augmented arterial marker expression as compared with exposure to constant shear. The expression of Gja5 correlated with arterial flow patterns: the redistribution of arterial flow provoked by vitelline artery ligation resulted in flow-driven collateral arterial network formation and was associated with increased expression of Gja5. In situ hybridization in normal and ligation embryos confirmed that Gja5 expression is confined to arteries and regulated by flow. In mice, Gja5 (connexin 40) was also expressed in arteries. In the adult, increased flow drives arteriogenesis and the formation of collateral arterial networks in peripheral occlusive diseases. Genetic ablation of Gja5 function in mice resulted in reduced arteriogenesis in two occlusion models. We conclude that pulsatile shear patterns may be central for supporting arterial identity, and that arterial Gja5 expression plays a functional role in flow-driven arteriogenesis.

John Calvin's Impact on Church and Society, 1509-2009. Essays for the 500th birthday of Calvin

A tribute to the monumental influence of John Calvin in the 500 years since his birth. / What legacies, still enduring today, have John Calvin and Calvinism given to the church and society in Europe and North America? An international group of scholars tackles that question in this volume honoring Calvin's 500th birthday. These chapters together provide a comprehensive and accessible introduction to Calvin's life and thought, the history of the Reformation in Switzerland and worldwide, and his continuing relevance for ecclesial, social, and political questions today. / Contributors: Philip Benedict, James D. Bratt, Emidio Campi, Wulfert de Greef, Christopher Elwood, Eva-Maria Faber, Eric Fuchs, Ulrich H. J. Krtner, Christian Link, Christian Moser, Andrew Pettegree, Christoph Strohm, Mario Turchetti./ The essays in this book fit beautifully together to provide a solid, complete work that gives precise insight into the many different facets of Calvin and Calvinism. The high-level research found here clearly shows the great impact that Calvin has had on both church and society. It is a great pleasure to see Calvin here anew. Eberhard Busch / University of Gttingen / That John Calvin made a deep and lasting impact on many aspects of history is common knowledge but the character of the man and the nature of his influence are perhaps as controversial as any that can be named. It is thus a challenge to examine even a fraction of the many ways that Calvins life and thought have contributed to the shaping of later ages in both church and society. This volume offers essays on key points from an appropriately international group of authors appreciative but critical, drawing on a rich range of recent scholarship, presented in a pleasing and accessible form. It is a fine place for the new reader of Calvin to get a glimpse of his impact, while offering a fresh summary of some significant issues for more advanced students of the Reformer. Elsie Anne McKee / Princeton Theological Seminary / Hirzel and Sallmann have succeeded in gathering essays by an illustrious circle of experts both historians and theologians on important areas of Calvins thought and impact. Ranging from an insignificant city at the edge of the Swiss Confederation in the 1530s to the Accra Confession of 2004, these essays will serve to correct popular misconceptions. A fine introduction for a broader readership that wants more than mere armchair theology. Peter Opitz / University of Zurich