oa Editorial [Hot topic: New Perspectives in Cardiovascular Medicine (Executive Editor: Jaye P.F. Chin-Dusting)]

Heart disease remains the leading cause of death in the United States and the main cause of heart disease is coronary artery disease [1]. This Special Issue on New Perspectives in Cardiovascular Medicine presents a series of reviews on potential new therapeutic targets for both vascular and cardiac pathologies. Unsurprisingly, given the powerful cardioprotective influence of endothelial cells, many of the reviews focus on targets located on this innermost layer of the vascular tree. The review by Fu and Zhu [2] examines the potential role of endothelial ectopic adenosine triphosphate synthase which is located in the endothelial cell plasma membrane and produces ATP which can bind to purinoceptors activating signalling pathways which regulate endothelial function. The capabilities of this protein structure range from the recruitment of inflammatory cells to the endothelium thus inducing vascular inflammation, to acting as a receptor for apolipoprotein A-1, implying a role for cholesterol metabolism, to the inhibition of prostacyclin synthesis and the enhancement of nitric oxide bioactivity. These capabilities render the molecule a strong target for atherosclerosis, hypertension and lipid disorders. Lumsden et al. [3] review the role of C-type natriuretic peptide, the paracrine element of the natriuretic peptide axis which plays such a fundamental role in cardiovascular homeostasis by modulating fluid and electrolyte balance and vascular tone. C-NP is produced by both endothelial and cardiac cells and Lumsden et al describe both its physiological and pathological roles in vascular and cardiac function exemplified by its control of blood flow in resistance vasculature and of pacemaker current in the heart as well as by its ability to protect against myocardial ischemic reperfusion injury. The authors thus suggest that pharmacological manipulation of the C-NP receptors, NPR-B and -C, hold promise in the advancement of treatment of cardiovascular disease such as heart failure, atherosclerosis and pulmonary hypertension. Asymmetric dimethylarginine (ADMA) is an endogenously produced molecule that inhibits nitric oxide synthase. The review by Arrigoni et al. [4] again focuses on manipulating endothelial function in cardiovascular pathologies, this time through the effects of both cellular and circulating ADMA on both nitric oxide dependent and independent pathways. The review further describes the role of dimethylarginine dimethylaminohydrolase (DDAH) in the metabolism of ADMA and a means by which the levels of ADMA can be modulated therapeutically to benefit such cardiovascular pathologies as hypertension, metabolic syndrome and diabetes. In the review on cytoprotection by natural and synthetic polyphenols by Jiang et al. [5], the authors discuss the therapeutic benefits of these molecules against myocardial injury following ischemia reperfusion. They describe that these cardiprotective effects have been attributed to anti-oxidant activities, preservation of nitric oxide, anti-inflammatory activities and modulation of matrix metalloproteinases as well as such novel mechanisms as the modulation of the function of enzymes involved in epigenetic modifications such as histone acetyltransferases. In addition, polyphenols may also be of therapeutic benefit against the development of cardiac hypertrophy, ventricular remodeling and fibrosis after myocardial infarction. Inflammation plays a fundamental role in atherosclerosis associated cardiovascular disease and adhesion of immune cells has a critical role in the inflammatory response and indeed the pathophysiology of this disorder. P-selectin is an inflammatory adhesion molecule which enables the recruitment of leukocytes to the endothelium and to activated platelets involved with the growing thrombus. It is thought to be critical in the progression of atherosclerosis and leukocyte recruitment to the plaque. The review by Woollard and Chin-Dusting [6] suggests that the targeting of P-selectin is a strong clinical candidate for developing novel therapeutic strategies in inflammatory diseases including atherosclerosis. Hagemeyer and Peter's review [7] on targeting platelet integrin GPIIb/IIIa revisits the critical role of this molecule in thrombus formation. Here the authors review current knowledge on GPIIb/IIa structure, signalling pathways and receptor function. Importantly, the positives and limitations of current anti-thrombotic compounds are also studied in detail with the view to learning from the successes and failures of GPIIb/IIIa blocker development towards making new and better improved blockers. Raising high density lipoproteins (HDL) is the focus of the review by Murphy et al. [8] which explores the complexities of such a task and why this potentially exciting therapeutic indication is still in its infancy with regards current understanding of the HDL metabolic pathway and all the implications thereof. The review comprehensively describes current and future HDL-raising medications and details the benefits and limitations of these. The review [9] by the late Sir James Black and his close collaborator and friend, Fitzgerald fittingly closes this Special Issues on New Perspectives in Cardiovascular Medicine - many of the contributors of whom are world-renowned in the respective fields. Sir James and Fitzgerald track through the historic detail in the discovery of the β-adrenoceptors and adrenergic system and focuses on its application in patients with congestive heart failure. Key to the review is that the different properties of β-blockers show the undesirability of β2- adrenoceptor activation and thus the rationale for the use of selective β2-adrenoceptor blockers is discussed. Together these reviews comprehensively illustrate the wealth of novel cardiovascular therapeutic targets for the better management of cardiovascular disease.