Schisandrol A (SA), one of the most abundant bioactive lignans extracted from the Schisandra chinensis (Turcz.) Baill., has multiple pharmacological properties. However, the underlying mechanisms of SA in protection against myocardial ischemia/reperfusion (MI/R) injury remain obscure. The present experiment was performed to explore the cardioprotective effects of SA in MI/R injury and hypoxia/reoxygenation- (H/R-) induced cardiomyocyte injury and clarify the potential underlying mechanisms. SA treatment significantly improved MI/R injury as reflected by reduced myocardium infarct size, attenuated histological features, and ameliorated biochemical indicators. In the meantime, SA could profoundly ameliorate oxidative stress damage as evidenced by the higher glutathione peroxidase (GSH-Px) as well as lower malondialdehyde (MDA) and reactive oxygen species (ROS). Additionally, SA alleviated myocardial apoptosis as evidenced by a striking reduction of cleaved caspase-3 expression and increase of Bcl-2/Bax ratio. Further experiments demonstrated that SA had certain binding capability to the key functional protein 14-3-3θ. Mechanistically, SA prevented myocardial apoptosis through upregulating 14-3-3θ expression. Interestingly, siRNA against 14-3-3θ could promote apoptosis of cardiomyocytes, and H/R injury after knockdown of 14-3-3θ could further aggravate apoptosis, while overexpression of 14-3-3θ could significantly reduce apoptosis induced by H/R injury. Further, 14-3-3θ siRNA markedly weakened the antiapoptotic role of SA. Our results demonstrated that SA could exert apparent cardioprotection against MI/R injury and H/R injury, and potential mechanisms might be associated with inhibition of cardiomyocyte apoptosis at least partially through upregulation of 14-3-3θ.
Background: Antithrombotic treatment for CAD patients undergoing PCI includes dual antiplatelet therapy comprising oral loading doses of 150-300 mg of acetylsalicylic acid and 300-600 mg of clopidogrel, followed by daily doses of 75-100 mg and 75 mg orally of each drug respectively. According to the literature about 6% of patients develop an allergic reaction to clopidogrel. In those cases it is recommended to switch therapy to a newer generation P2Y12 platelet receptor blocker: prasugrel or ticagrelor, due to their quicker onset of action and more potent platelet aggregation inhibition. Our aim was to compare the annual cost of newer antiplatelet drugs versus outpatient oral clopidogrel desensitization procedure followed by clopidogrel therapy. Material and Methods: We calculated the yearly price of ticagrelor therapy for one patient by using the publicly available prices of DDD in Croatia (ESC guidelines for antithrombotic treatment in CAD patients undergoing PCI) to be 813.4€ (prasugrel is not reimbursed in Croatia), while one year of clopidogrel therapy including the cost of outpatient oral clopidogrel desensitization procedure (3 half-day clinical visits) amounted to 289.51€. Results: Approximately 6529 patients undergo PCI procedures in Croatia per year and 6% of them develop allergy to clopidogrel. Yearly savings would amount to 205,244.38€ if those patients would stay on clopidogrel after successfully (90%) completing oral clopidogrel desensitization rather than be started on ticagrelor. Conclusions: Since annual therapy with clopidogrel, even with desensitization, is 2.8 times cheaper than ticagrelor treatment, we believe that it would be more cost effective for patients with clopidogrel allergy who cannot afford copayment for a newer generation platelet aggregation inhibitor.
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