11 research outputs found
Mice lacking the CĪ² subunit of PKA are resistant to angiotensin II-induced cardiac hypertrophy and dysfunction
<p>Abstract</p> <p>Background</p> <p>PKA is a ubiquitous, multi-subunit cellular kinase that regulates a number of different physiological responses in response to cAMP, including metabolism, cell division, and cardiac function. Numerous studies have implicated altered PKA signaling in cardiac dysfunction. Recently, it has been shown that mice lacking the catalytic Ī² subunit of PKA (PKA CĪ²) are protected from age-related problems such as weight gain and enlarged livers, and we hypothesized that these mice might also be resistant to cardiomyopathy.</p> <p>Findings</p> <p>Angiotensin II (ang II) induced hypertension in both PKA CĪ² null mice and their WT littermates. However, PKA CĪ² null mice were resistant to a number of ang II-induced, cardiopathological effects observed in the WT mice, including hypertrophy, decreased diastolic performance, and enlarged left atria.</p> <p>Conclusion</p> <p>The CĪ² subunit of PKA plays an important role in angiotensin-induced cardiac dysfunction. The CĪ² null mouse highlights the potential of the PKA CĪ² subunit as a pharmaceutical target for hypertrophic cardiac disease.</p
Estimating the Cost of Social-Democratic Government by Regression-Discontinuity Analysis of Close Elections
ABSTRACT: This paper employs a regression-discontinuity (RD) design to ascertain the effects of social-democratic government on fiscal policy (budget deficits) and monetary policy (as reflected in inflation) and on currency and bond prices (i.e., exchange rates and yields). The RD design exploits the essentially random application of a treatmentāin this case, social-democratic parties gaining governmentānear a discontinuous break in the probability of receiving that treatmentāin this case, a discontinuous rise in the probability of entering government occurs as the social-democratic party seat-share crosses the plurality thresholdāto identify and estimate the causal effect of the treatment (social-democratic government). One advantage of the RD design for researching these questions is that RD does not require, as have previously employed strategies, strong assumptions about if, how, or when market actors form political expectations, or about the quality and dissemination of political information, or about functional forms or explanatory-variable selection. Instead, the strategy relies on balancing observed and unobserved characteristics of the cases near the discontinuity on either side. Our findings suggest no or small and insignificant partisan-government effects except for a small and very short-term (one month), but statistically significant, currency-depreciation resulting from assumption of governmental power of social-democratic parties following close elections.1 I. Introduction and Motivation
Simvastatin provides longāterm improvement of left ventricular function and prevents cardiac fibrosis in muscular dystrophy
Abstract Duchenne muscular dystrophy (DMD), caused by absence of the protein dystrophin, is a common, degenerative muscle disease affecting 1:5000 males worldwide. With recent advances in respiratory care, cardiac dysfunction now accounts for 50% of mortality in DMD. Recently, we demonstrated that simvastatin substantially improved skeletal muscle health and function in mdx (DMD) mice. Given the known cardiovascular benefits ascribed to statins, the aim of this study was to evaluate the efficacy of simvastatin on cardiac function in mdx mice. Remarkably, in 12āmonth old mdx mice, simvastatin reversed diastolic dysfunction to normal after shortāterm treatment (8Ā weeks), as measured by echocardiography in animals anesthetized with isoflurane and administered dobutamine to maintain a physiological heart rate. This improvement in diastolic function was accompanied by increased phospholamban phosphorylation in simvastatinātreated mice. Echocardiography measurements during longāterm treatment, from 6Ā months up to 18Ā months of age, showed that simvastatin significantly improved inĀ vivo cardiac function compared to untreated mdx mice, and prevented fibrosis in these very old animals. Cardiac dysfunction in DMD is also characterized by decreased heart rate variability (HRV), which indicates autonomic function dysregulation. Therefore, we measured cardiac ECG and demonstrated that shortāterm simvastatin treatment significantly increased heart rate variability (HRV) in 14āmonthāold conscious mdx mice, which was reversed by atropine. This finding suggests that enhanced parasympathetic function is likely responsible for the improved HRV mediated by simvastatin. Together, these findings indicate that simvastatin markedly improves cardiac health and function in dystrophic mice, and therefore may provide a novel approach for treating cardiomyopathy in DMD