Cardiometabolic interventions - focus on transcriptional regulators

Cardiovascular disease (CVD) remains the largest healthcare burden in the Western world; and the increasing prevalence of type II diabetes mellitus, at least partially driven by a trend in lifestyle changes associated with global economic development, is likely to fuel this CVD burden worldwide. Over the past two decades, there has been an increased awareness of the convergence of risk factors contributing to both cardiovascular disease and diabetes leading to the concept of the metabolic syndrome, and the realisation of the opportunity to intervene at this intersection to simultaneously target CVD and metabolic dysfunction. This brings together the fields of cardiovascular medicine, diabetology, and increasingly clinical immunology for a unified and concerted effort to reduce risk for both conditions simultaneously. The discovery of the targeted pathways of drugs already in clinical use such as fibrates and thiazolidinediones (TZD) has led to accelerated basic and clinical research into selective and dual PPAR-α and PPAR-γ agonists, which can theoretically target glucose, lipid and lipoprotein metabolism, as well as potentially exerting inhibitoryeffects in vascular inflammation, all of which might be predicted to reduce atherosclerosis. In this article, we will discuss the basic science as well as recent clinical development in the pursuit of optimal cardiometabolic intervention along with insight into strategies for future drug development.