RATIONALE Phospholamban (PLN) is an inhibitor of cardiac sarco(endo)plasmic reticulum Ca²⁺ ATPase. PLN knockout (PLN-KO) enhances sarcoplasmic reticulum Ca²⁺ load and Ca²⁺ leak. Conversely, PLN-KO accelerates Ca²⁺ sequestration and aborts arrhythmogenic spontaneous Ca²⁺ waves (SCWs). An important question is whether these seemingly paradoxical effects of PLN-KO exacerbate or protect against Ca²...

INTRODUCTION Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the ST2 receptor. Previous work suggested implication of the IL-33/ST2 axis in the pathogenesis of human and mouse arthritis. Here, we directly investigated the role of endogenous IL-33 in K/BxN serum transfer-induced arthritis by using IL-33 knockout (KO) mice. METHODS Arthritis was induced by injection ...

Collecting duct (CD)-derived endothelin-1 (ET-1) exerts natriuretic, diuretic, and hypotensive effects. In vitro studies have implicated cyclooxygenase (COX) metabolites, and particularly PGE(2), as important mediators of CD ET-1 effects. However, it is unknown whether PGE(2) mediates CD-derived ET-1 actions in vivo. To test this, CD ET-1 knockout (KO) and control mice were studied. During norm...

Caveolin-1 (Cav-1) is essential for the morphology of membrane caveolae and exerts a negative influence on a number of signaling systems, including nitric oxide (NO) production and activity of the MAP kinase cascade. In the vascular system, ablation of caveolin-1 may thus be expected to cause arterial dilatation and increased vessel wall mass (remodeling). This was tested in Cav-1 knockout (KO)...