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Objectives: We studied the signal transduction of atrial structural remodeling that contributes to the pathogenesis of atrial fibrillation (AF). Background: Fibrosis is a hallmark of arrhythmogenic structural remodeling, but the underlying molecular mechanisms are incompletely understood. Methods: We performed transcriptional profiling of left atrial myocardium from patients with AF and sinus rhythm and applied cultured primary cardiac cells and transgenic mice with overexpression of constitutively active V12Rac1 (RacET) in which AF develops at old age to characterize mediators of the signal transduction of atrial remodeling. Results: Left atrial myocardium from patients with AF showed a marked up-regulation of connective tissue growth factor (CTGF) expression compared with sinus rhythm patients. This was associated with increased fibrosis, nicotinamide adenine dinucleotide phosphate oxidase, Rac1 and RhoA activity, up-regulation of N-cadherin and connexin 43 (Cx43) expression, and increased angiotensin II tissue concentration. In neonatal rat cardiomyocytes and fibroblasts, a specific small molecule inhibitor of Rac1 or simvastatin completely prevented the angiotensin II–induced up-regulation of CTGF, Cx43, and N-cadherin expression. Transfection with small-inhibiting CTGF ribonucleic acid blocked Cx43 and N-cadherin expression. RacET mice showed up-regulation of CTGF, Cx43, and N-cadherin protein expression. Inhibition of Rac1 by oral statin treatment prevented these effects, identifying Rac1 as a key regulator of CTGF in vivo. Conclusions: The data identify CTGF as an important mediator of atrial structural remodeling during AF. Angiotensin II activates CTGF via activation of Rac1 and nicotinamide adenine dinucleotide phosphate oxidase, leading to up-regulation of Cx43, N-cadherin, and interstitial fibrosis and therefore contributing to the signal transduction of atrial structural remodeling. [Copyright &y& Elsevier]

Objectives: We aimed to study the role of Rac1 GTPase in atrial fibrillation (AF). Background: The signal transduction associated with AF is incompletely understood. We hypothesized that activation of Rac1 GTPase contributes to the pathogenesis of AF via activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and production of reactive oxygen species. Methods: Old mice with cardiac-specific overexpression of constitutively active V12Rac1 (RacET) were compared with wild-type (WT) and WT undergoing transaortic constriction (TAC). In addition, samples of human left atrial appendages were analyzed in patients with sinus rhythm (SR) compared with patients with permanent AF matched for atrial diameter. Results: At age 16 months, 75% of RacET but no WT or TAC mice showed AF. Treatment of RacET with statins for 10 months did not alter weight or fibrosis of atria or ventricles but decreased cardiac Rac1 and NADPH oxidase activity and reduced the incidence of AF by 50%. The left atria of patients with AF showed increased fibrosis, up-regulation of NADPH oxidase activity, a 4-fold increase of Rac1 total protein and membrane expression as well as up-regulation of Rac1 activity. Conclusions: Chronic cardiac overexpression of Rac1 represents a novel mouse model for AF. Rac1 GTPase contributes to the pathogenesis of AF and identifies a target for the prevention and treatment of AF. [Copyright &y& Elsevier]

Investigates the down-regulation of Rac-1 guanosine triphosphatase (GTPase) by estrogen. Testing of the hypothesis that 17beta-estradiol may regulate Rac1 guanosine triphosphate (GTPase) expression and activity and inhibit the release of reactive oxygen species (ROS) from VSMC; Finding that Racl GTPase gene-transcription and activity is regulated by 17beta-estradiol.

This study examines the potential of open-ended student drawing serving as a springboard for creative performance and innovative ways of knowing in undergraduate biology. Our methodology takes into consideration visual stimuli (images on the instructor's PowerPoint slides), students' responses to an open-ended drawing task, and the sociocultural context in which these drawings were produced. Our visual design analysis revealed that nearly 40% of students (n = 20/52) opted for creatively reinventing science examples in a manner that was highly original and novel. It is argued that open-ended drawing can help open the doors of science instruction to student creativity and creative performance. • Open-ended drawing can help make room for creativity in science. • Nearly 40% of students creatively reinvented science examples in an imaginative manner. • Students explored innovative alternatives to visual representation of concepts. [ABSTRACT FROM AUTHOR]

Background: We studied the role of the mineralocorticoid receptor (MR) for atrial fibrotic remodeling. Results: Increased 11β-hydroxysteroid dehydrogenase type 2 in atrial fibrillation enhances mineralocorticoid receptor pro- fibrotic signaling through connective tissue growth factor, lysyl oxidase, and microRNA-21. Conclusion: The MR regulates fibrogenesis in atrial fibrillation. Significance: The MR may represent a target for the prevention of atrial fibrosis. [ABSTRACT FROM AUTHOR]