Cyclic Nucleotide Phosphodiesterases and Compartmentation in Normal and Diseased Heart

International audienceCyclic nucleotide phosphodiesterases (PDEs) degrade the second messengers cAMP and cGMP, thereby regulating multiple aspects of cardiac function. This highly diverse class of enzymes encoded by 21 genes encompasses 11 families which are not only responsible for the termination of cyclic nucleotide signalling, but are also involved in the generation of dynamic microdomains of cAMP and cGMP controlling specific cell functions in response to various neurohormonal stimuli. In myocardium, the PDE3 and PDE4 families are predominant to degrade cAMP and thereby regulate cardiac excitation-contraction coupling. PDE3 inhibitors are positive inotropes and vasodilators in human, but their use is limited to acute heart failure and intermittent claudication. PDE5 is particularly important to degrade cGMP in vascular smooth muscle, and PDE5 inhibitors are used to treat erectile dysfunction and pulmonary hypertension. However, these drugs do not seem efficient in heart failure with preserved ejection fraction. There is experimental evidence that these PDEs as well as other PDE families including PDE1, PDE2 and PDE9 may play important roles in cardiac diseases such as hypertrophy and heart failure. After a brief presentation of the cyclic nucleotide pathways in cardiac cells and the major characteristics of the PDE superfamily, this chapter will present their role in cyclic nucleotide compartmentation and the current use of PDE inhibitors in cardiac diseases together with the recent research progresses that could lead to a better exploitation of the therapeutic potential of these enzymes in the future

Youth unemployment and employment trajectories in Spain during the Great Recession: what are the determinants?

Since the beginning of the recession period in Europe, unemployment has greatly affected the young adult population. In this context, Spain is regarded as an extreme case, due to its exceptionally high youth unemployment rates. This article seeks to identify the determinants that have led certain groups of Spanish young people to suffer labour market trajectories with higher levels of unemployment and instability during the Great Recession than others. To do this, retrospective data from the 2012 Catalan Youth Survey are used. With these data and using cluster analysis, a typology of labour market trajectories is constructed. Next, multinomial logistic regressions are used to identify what individual socio-demographic characteristics and pre-crisis employment experiences are connected to these different typological career paths. Results show that the highly differentiated career paths are associated with different social profiles and differences in the presence of unemployment. Moreover, interesting differences among the most unstable career paths appear. For the most vulnerable social profiles the employment trajectory prior to the crisis seems to point towards the existence of an entrapment in low-skilled jobs that alternate with situations of unemployment. For those with a slightly better position their employment situation after the initiation of the crisis seems to have been impacted by their brief labour market trajectory before the crisis and their resulting work experience gap.We would like to thank the Catalan Youth Observatory for letting us use the data from the Catalan Youth Survey 2012. We would particularly like to thank Pau Serracant for his help and for encouraging us to send our study to the Journal of Labour Market Research in response to their call for research on Youth unemployment in Europe. We are also grateful to two anonymous referees for their comments, which enabled us to greatly improve the quality of our paper. It goes without saying that any errors in this article are the sole responsibility of the authors