Yanjie Lu

Resveratrol protects against arsenic trioxide-induced cardiotoxicity in vitro and in vivo

Background and purpose: The clinical use of arsenic trioxide (As2O3), a potent antineoplastic agent, is limited by its severe cardiotoxic effects. QT interval prolongation and apoptosis have been implicated in the cardiotoxicity of As2O3. The present study was designed to evaluate the effects of resveratrol on As2O3‐induced apoptosis and cardiac injury.

Scutellarin-induced endothelium-independent relaxation in rat aorta

Scutellarin is a flavonoid extracted from the traditional Chinese herb, Erigeron breviscapus Hand Mazz. In the present study, the vasorelaxant effects of scutellarin and the underlying mechanism were investigated in isolated rat aorta. Scutellarin (3, 10, 30, 100 µm) caused a dose‐dependent relaxation in both endothelium‐intact and endothelium‐denuded rat aortic rings precontracted with noradrenaline bitartrate (IC50 = 7.7 ± 0.6 µm), but not with potassium chloride. Tetraethylammonium, glibenclamide, atropine, propranolol, indomethacin and N(G)‐nitro‐l‐arginine methyl ester had no influence on the vasorelaxant effect of scutellarin, which further excluded the involvement of potassium channels, muscarinic receptor, nitric oxide pathway and prostaglandin in this effect. Pretreatment with scutellarin decreased the tonic phase, but not the phasic phase of the noradrenaline bitartrate induced tension increment. Scutellarin also alleviated Ca2+‐induced vasoconstriction in Ca2+‐depleted/noradrenaline bitartrate pretreated rings in the presence of voltage‐dependent calcium channel blocker verapamil. The noradrenaline bitartrate evoked intracellular calcium increase was inhibited by scutellarin. Scutellarin had no effect on phorbol‐12,13‐diacetate induced contraction in a calcium‐free bath solution. These results showed that scutellarin could relax thoracic artery rings in an endothelium‐independent manner. The mechanism seems to be the inhibition of extracellular calcium influx independent of the voltage‐dependent calcium channel. Copyright

Arsenic Trioxide-Induced Apoptosis in H9c2 Cardiomyocytes: Implications in Cardiotoxicity

Arsenic trioxide (As(2)O(3)) achieved dramatic remissions in patients with acute promyelocytic leukaemia. Clinical reports have shown that treatment was associated with cardiotoxicity. We investigated the toxic mechanisms of As(2)O(3) in H9c2 cardiomyocytes. Clinically relevant concentrations of As(2)O(3) (2-10 microM) reduced the viability of H9c2 cells in a concentration-dependent manner. The decreased cell viability was because As(2)O(3) induced cell apoptosis (cell shrinkage, nuclear alterations and caspase-3 activation), or even necrosis at higher concentrations. Inhibition of caspase-3 with a specific inhibitor, Ac-DEVD-CHO, suppressed apoptosis induced by As(2)O(3). In addition, reactive oxygen species formation and cellular Ca(2+) overload were observed in H9c2 cells exposed to As(2)O(3), which was partly inhibited by vitamin E and verapamil. These results suggest that As(2)O(3)-induced cardiotoxicity is mediated, at least in part, by activation of caspase-3 pathway, which may be triggered by reactive oxygen species formation and intracellular Ca(2+) overload.

Advances in exploring the role of microRNAs in the pathogenesis, diagnosis and therapy of cardiac diseases in China

Cardiovascular disease has become the most serious health threat and represents the major cause of morbidity and mortality in China, as in other industrialized nations. During the past few decades, Chinas economic boom has tremendously improved peoples standard of living but has also changed their lifestyle, increasing the prevalence of cardiovascular disease, the so‐called ‘disease of modern civilization’. This new trend has attracted a significant amount of research. Many of the studies conducted by Chinese investigators are orientated towards understanding the molecular mechanisms of cardiovascular disease. At the molecular level, the long‐standing consensus is that cardiovascular disease is associated with a sequence mutation (genetic anomaly) and expression deregulation (epigenetic disorder) of protein‐coding genes. However, new research data have established the non‐protein‐coding genes microRNAs (miRNAs) as a central regulator of the pathogenesis of cardiac disease and a potential new therapeutic target for cardiovascular disease. These small non‐coding RNAs have also been subjected to extensive, rigorous investigations by Chinese researchers. Over the years, a large body of studies on miRNAs in cardiovascular disease has been conducted by Chinese investigators, yielding fruitful research results and a better understanding of miRNAs as a new level of molecular mechanisms for the pathogenesis of cardiac disease. In this review, we briefly summarize the current status of research in the field of miRNAs and cardiovascular disease in China, highlighting the advances made in elucidating the role of miRNAs in various cardiac conditions, including cardiac arrhythmia, myocardial ischaemia, cardiac hypertrophy and heart failure. We have also examined the potential of miRNAs as novel diagnostic biomarkers and therapeutic targets.