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Background Doxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main limitation of its clinical application. Purpose The present study investigated the potential protective effect of sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, against DOX-induced cardiotoxicity in rats and H9c2 cells, and whether the underlying mechanism for any such protection involves its antioxidant activity. Methods Male Sprague-Dawley rats were randomly divided into four groups: DOX (1.5 mg/kg/day intraperitoneally for 10 days), DOX+valsartan (31 mg/kg/day by gavage from day 1 to day 18), DOX+sacubitril/valsartan (68 mg/kg/day by gavage from day 1 to day 18), and control (saline intraperitoneally for 10 days). There were 15 rats in each group. At the end of the treatment period, samples were collected and analysed. Cardiac function, tissue morphology, and reactive oxygen species (ROS) were evaluated in rats. Serum levels of Malondialdehyde (MDA) and cardiac troponin T were also measured. Mitochondrial ROS production and cell viability were evaluated in H9c2 cells. Results DOX-induced cardiac dysfunction was not prevented by valsartan and sacubitril/valsartan in this model. However, the serum level of cardiac troponin T on day 18 was increased in the DOX group (0.046±0.006 ng/mL, p Conclusions Sacubitril/valsartan protected rat hearts from DOX-induced cardiotoxicity in vivo and in vitro by decreasing oxidative stress. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This work was supported by Novartis Pharma K.K.

Background For the prevention of future cardiovascular events, control of residual risks such as triglyceride rich lipoproteins and HDL-cholesterol is an emerging problem beyond LDL-cholesterol. Triglyceride to HDL-cholesterol ratio (TG/HDL ratio) has been reported to be useful for risk classification of cardiovascular diseases. Meanwhile, several studies showed that high-risk plaque characteristics evaluated with coronary CT angiography (cCTA) was associated with the incidence of acute coronary syndrome. However, the relationship of TG/HDL ratio with coronary plaque characteristics and its impact of this association on future coronary events have not been fully elucidated. Purpose The aim of this study was to evaluate the association between TG/HDL ratio and high-risk plaque detected by cCTA and its impact on future coronary events. Methods A total of 944 patients suspected stable coronary artery disease who underwent cCTA at our institution were analyzed (mean 64-year-old, 55% male). Patients were divided into two groups by the median value of TG/HDL ratio (higher TG/HDL: TG/HDL ratio ≥2.0, lower TG/HDL: TG/HDL ratio 1.1) and spotty calcification. Cardiovascular event was defined as cardiovascular death, acute coronary syndrome, and late coronary revascularization after 30 days of CT acquisition. Results The higher TG/HDL ratio was significantly associated with male gender (63% vs. 48%, P Conclusion TG/HDL ratio is involved in the vulnerability of CT-verified coronary plaque characteristics. This association may play an important role in the prognostic impact of TG/HDL ratio on future cardiovascular events. Funding Acknowledgement Type of funding source: None

Background Abdominal aortic aneurysm (AAA) is a life-threatening disease, while effective and preventive medical treatments remain unestablished. Purpose The aim of this study was to evaluate the effect of selective peroxi- some proliferator-activated receptor alpha (PPARα) modulator pemafibrate on AAA formation in mice. Methods AAA was induced by subcutaneous infusion of angiotensin II (AngII) in apolipoprotein E-deficient mice for 4 weeks. Treatment by pemafibrate or vehicle was started one week before AngII infusion. Oxidative stress was evaluated by dihydroethidium (DHE) staining. Results Prognosis after AngII infusion in pemafibrate-treated mice was significantly better than that in vehicle-treated mice (log-rang test, p=0.035) by reducing the occurrence of fatal AAA rupture. Meanwhile pemafibrate did not significantly reduce maximal diameter of the aorta. Histological findings demonstrated that the expression of collagen in adventitia in pemafibrate-treated mice was significantly greater than that in vehicle-treated mice (p Conclusion Pemafibrate reduced the rupture of AAA in this murine model, which is associated with anti-oxidative stress via catalase induction. Funding Acknowledgement Type of funding source: None