Cardioprotective growth factors

Abstract

Many of the originally identified cardiovascular 'growth factors' have been demonstrated to exert a diverse variety of actions within the cardiovascular system, the majority of which are unrelated to their initially proposed mechanism of action. Interestingly, several of these growth factors have been demonstrated to protect the cardiomyocyte from the detrimental effects of acute ischaemia-reperfusion injury, through the activation of a variety of cell-surface receptors and the subsequent recruitment of a number of intracellular signal transduction pathways, which include components of the reperfusion injury salvage kinase pathway. This article will review several of these cardioprotective growth factors with respect to their ability to confer direct myocardial protection, focusing on the underlying signalling pathways involved and their potential for clinical application.

Role of adipokines in cardiovascular disease

“…It has also been demonstrated to have a detrimental effect on I/R injury in isolated perfused rat hearts (Rothwell et al 2006) -although this effect is disputed by other studies . Resistin counteracts the beneficial effects of insulin, a cardioprotective agent (Hausenloy & Yellon 2009). Rothwell et al (2006) found resistin to worsen cardiac I/R injury in rat hearts preconditioned with resistin.…”

Cardiotoxicity mechanisms of the combination of BRAF-inhibitors and MEK-inhibitors

“…The activation of RAF isoforms then stimulated the MEK/ ERK downstream. Bronte, Bronte, Novo, Pernice, et al, 2015;Hausenloy & Yellon, 2009;Zachary, 2001).…”

Cardiac Postconditioning: An Additional Therapy to Limit Cell Death Following Myocardial Infarction

“…In ischemic postconditioning, the RISK pathway is activated at the onset of reperfusion by cell surface receptors including G-protein coupled receptors, cytokine receptors, tyrosine kinase receptors and serine/threonine receptors (Hausenloy and Yellon 2009). Adenosine receptors (Morrison et al 2007) and sphingosine kinase-1 receptors (Jin et al 2008) activate the RISK pathway and it is probable that many other cell-surface implicated as triggers in ischemic postconditoning, such as bradykinin and opioids receptors, also activate the RISK pathway but this remains to be demonstrated directly.…”

“…Interestingly, although a large number of potential anti-apoptotic pathways exist downstream of the RISK pathway, relatively few have actually been investigated in the context of cardioprotection, yet alone ischemic postconditioning. These anti-apoptotic mechanisms include: the phosphorylation and inhibition of pro-apoptotic proteins such as BAD (Bcl-2 antagonist of cell death) (Jonassen et al 2001), BAX (Bcl-2-associated X protein) and the activation of anti-apoptotic proteins such as PIM-1 kinase (Hausenloy and Yellon 2009), the effect of which is preservation of mitochondrial integrity and a favorable increase i n t h e a n t i -a p o p t o t i c p r o t e i n s s u c h a s B C L2 (B-cell lymphoma-2) and BCL-XL (B-cell lymphoma-xl). …”