Ghrelin mediated cardioprotection using in vitro models of oxidative stress.

Ghrelin is commonly known as the 'hunger hormone' due to its role in stimulating food intake in humans. However, the roles of ghrelin extend beyond regulating hunger. Our aim was to investigate the ability of ghrelin to protect against hydrogen peroxide (H2O2), a reactive oxygen species commonly associated with cardiac injury. An in vitro model of oxidative stress was developed using H2O2 injured H9c2 cells. Despite lentiviral ghrelin overexpression, H9c2 cell viability and mitochondrial function were not protected following H2O2 injury. We found that H9c2 cells lack expression of the preproghrelin cleavage enzyme prohormone convertase 1 (encoded by PCSK1), required to convert ghrelin to its active form. In contrast, we found that primary rat cardiomyocytes do express PCSK1 and were protected from H2O2 injury by lentiviral ghrelin overexpression. In conclusion, we have shown that ghrelin expression can protect primary rat cardiomyocytes against H2O2, though this effect was not observed in other cell types tested.

New Developments in Cardiac Regeneration.

Numerous pharmacological and device therapies have improved adverse cardiac remodelling and mortality in heart failure. However, none are able to regenerate damaged cardiac tissue. Stem cell based therapies using multipotent (adult) stem cells and pluripotent stem cells are new approaches that could potentially achieve the elusive goal of true cardiac regeneration. Over the past two decades, various stem cell based approaches have been shown to improve left ventricular function in pre-clinical animal models. Promising results rapidly led to clinical trials, initially using bone marrow-derived mononuclear cells, then mesenchymal stromal cell populations and, more recently, progenitor cells from the adult heart itself. These have been shown to be safe and have advanced our understanding of potential suitable recipients, cell delivery routes, and possible mechanisms of action. However, efficacy in these trials has been inconsistent. Human pluripotent stem cells (hPSCs) are another potential source of stem cells for cardiac regeneration. They could theoretically provide an unlimited source of cardiomyocytes or cardiac progenitors. Pre-clinical studies in both small and large animal models have shown robust engraftment and improvements in cardiac function. The first clinical trial using hPSC-derived cardiac derivatives has now commenced and others are imminent. In this brief review article, we summarise recent developments in stem cell therapies aimed at cardiac regeneration, including discussion of types of cell and non-cell-based strategies being explored.

Stem cell therapy for cardiac dysfunction.

Following significant injury, the heart undergoes induced compensation and gradually deteriorates towards impending heart failure. Current therapy slows but does not halt the resultant adverse remodeling. Stem cell therapy, however, has the potential to regenerate or repair infarcted heart tissue and therefore is a promising therapeutic strategy undergoing intensive investigation. Due to the wide range of stem cells investigated, it is difficult to navigate this field. This review aims to summarize the main types of stem cells (both of cardiac and extra-cardiac origin) that possess promising therapeutic potential. Particular focus is placed on clinical trials supporting this therapeutic strategy.

HIT: nucleic acid masquerading as heparin.

In this issue of Blood, Jaax and colleagues show that heparin-PF4 antibodies cross-reacted with nucleic acid (NA)­PF4 complexes and induced platelet activation, suggesting that NA-PF4 can potentially cause a heparin-induced thrombocytopenia (HIT)­like prothrombotic disorder.