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

Exercise mediated protection of diabetic heart through modulation of microRNA mediated molecular pathways

Abstract Hyperglycaemia, hypertension, dyslipidemia and insulin resistance collectively impact on the myocardium of people with diabetes, triggering molecular, structural and myocardial abnormalities. These have been suggested to aggravate oxidative stress, systemic inflammation, myocardial lipotoxicity and impaired myocardial substrate utilization. As a consequence, this leads to the development of a spectrum of cardiovascular diseases, which may include but not limited to coronary endothelial dysfunction, and left ventricular remodelling and dysfunction. Diabetic heart disease (DHD) is the term used to describe the presence of heart disease specifically in diabetic patients. Despite significant advances in medical research and long clinical history of anti-diabetic medications, the risk of heart failure in people with diabetes never declines. Interestingly, sustainable and long-term exercise regimen has emerged as an effective synergistic therapy to combat the cardiovascular complications in people with diabetes, although the precise molecular mechanism(s) underlying this protection remain unclear. This review provides an overview of the underlying mechanisms of hyperglycaemia- and insulin resistance-mediated DHD with a detailed discussion on the role of different intensities of exercise in mitigating these molecular alterations in diabetic heart. In particular, we provide the possible role of exercise on microRNAs, the key molecular regulators of several pathophysiological processes