The case for inhibiting p38 mitogen-activated protein kinase in heart failure

This minireview discusses the evidence that the inhibition of p38 mitogen-activated protein kinases (p38 MAPKs) maybe of therapeutic value in heart failure. Most previous experimental studies, as well as past and ongoing clinical trials, have focussed on the role of p38 MAPKs in myocardial infarction and acute coronary syndromes. There is now growing evidence that these kinases are activated within the myocardium of the failing human heart and in the heart and blood vessels of animal models of heart failure. Furthermore, from a philosophical viewpoint the chronic activation of the adaptive stress pathways that lead to the activation of p38 MAPKs in heart failure is analogous to the chronic activation of the sympathetic, renin-aldosterone-angiotensin and neprilysin systems. These have provided some of the most effective therapies for heart failure. This minireview questions whether similar and synergistic advantages would follow the inhibition of p38 MAPKs

The TAB1-p38α complex aggravates myocardial injury and can be targeted by small molecules

This paper explores the question of identity formation in the blogosphere (that is, do bloggers identify as such) from the perspective of a cultural history of blog technologies, incorporating the early origins of internet technologies

The role of redox signalling in cardiovascular regeneration

© Springer Nature Singapore Pte Ltd. 2019. Cardiovascular disease (CVD) is a major public health problem, particularly in the industrialised world, with diverse causes. Central to these underlying aetiologies is a progressive loss of functional cardiomyocytes, maladaptive remodelling, and resultant cardiac dysfunction. The ageing heart is characterised by perturbations in numerous signalling pathways, impairing its ability to repair and replace injured cardiomyocytes. This is caused at least in part by dysregulation of redox signalling- both in regard to production of reactive oxygen species (ROS), and disruption of cellular protective mechanisms. Cardiac regeneration is one area of particular therapeutic promise, which seeks to ameliorate cardiac function by either (1) direct application of stem cells, (2) modification of molecular signalling pathways to restore the endogenous reparative capacity of the heart, or (3) a combination of these two approaches. Unravelling these molecular and cellular signalling pathways is paramount to unlocking the potential of cardiac regenerative therapies, and theoretically revolutionising the medical management of patients with heart failure. In this chapter, we will review the role of oxidative stress in cardiovascular disease, and the pathophysiological molecular signalling pathways that are involved in the transition from young to ageing heart. We will then provide an overview of the molecular therapies that are used to target these pathways to enhance heart regeneration, future directions involving cellular and novel ‘bio-printing’ based approaches, in addition to current promising clinical trials