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We previously reported a novel danshensu derivative (R)-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (ADTM) that exhibited promising cardiovascular protective activities, such as antioxidant and antiplatelet activities, as well as arterial relaxation. Particularly, ADTM treatment for 24 h exhibited anti-oxidative activity and effectively protected against acute myocardial infarction (MI) in a rat model. Here, we further investigated the pharmacological actions of 14 days of treatment with ADTM in alleviating and restoring the MI size by stimulating revascularization. The pro-angiogenesis activity of ADTM has been validated in multiple experimental models including MI mouse, zebrafish, human umbilical vein endothelial cells (HUVECs) and A7r5 vascular smooth muscle cells (VSMCs). In addition, the effect of ADTM on L-type Ca 2 + current ( I CaL ) was determined. We demonstrated that ADTM (12–24 mg/kg) treatment for 14 days significantly decreased myocardial infarct size, increased the blood vessel density compared to vehicle in the myocardial peri-infarct area, and ADTM (24 mg/kg) enhanced the serum VEGF level in MI mice ( P < 0.05). We also demonstrated that treatment with ADTM at 50–200 μM rescued chemical-induced blood vessel loss in zebrafish. Although ADTM did not directly promote the features of angiogenesis in HUVECs, ADTM significantly increased VEGF production in a dose-dependent manner in A7r5 cells ( P < 0.05). A patch clamp experiment demonstrated that ADTM (200 μM) inhibited I CaL at all depolarizing voltages, with > 50% inhibition at + 10 mV. Taken together, our results indicated that ADTM served as a Ca 2+ current blocker, promoted angiogenesis and reduced experimental myocardial infarct size in mice, probably through stimulation of VEGF production in VSMCs. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of liraglutide in patients with Type 2 Diabetes Mellitus (T2DM) complicated with Coronary Artery Disease (CAD), we searched PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Wanfang Database and Chinese Biomedical Literature database (CBM) for relevant randomized controlled trials (RCTs) from inception to 7 October 2020. A total of 18 RCTs including 1557 patients with T2DM complicated with CAD were included. Meta-analysis revealed liraglutide reduced hemoglobin A1c (HbA1c) (WMD = −0.67; 95% CI[−0.94 to −0.39]; P < 0.00001), fasting plasma glucose (FPG) (WMD = −0.80; 95% CI[−1.06 to −0.54]; P < 0.00001) and 2 h plasma glucose (2hPG) (WMD = −1.64; 95% CI[−2.12 to −1.16]; P ＜0.00001); improved left ventricular ejection fraction(LVEF) (WMD = 4.79; 95% CI[4.08–5.51]; P < 0.00001), left ventricular end-diastolic diameter (LVEDD) (WMD = −5.70; 95% CI[−6.67 to −4.72]; P ＜0.00001), E/A (WMD = 0.13; 95% CI[0.11–0.14]; P < 0.00001) and left ventricular posterior wall thickness (LVPWT) (WMD = −1.86; 95% CI[−2.16 to −1.55]; P < 0.00001); reduced total cholesterol (TC) (WMD = −0.48; 95% CI[−0.56 to −0.39]; P < 0.00001), triglycerides (TG) (WMD = −0.42; 95% CI[−0.59 to −0.26]; P < 0.00001), low-density lipoprotein cholesterol (LDL-C) (WMD = −0.41; 95% CI[−0.55 to −0.26]; P < 0.00001), and increased high-density lipoprotein cholesterol (HDL-C) (WMD = −0.19; 95% CI[0.13–0.24]; P = 0.0005). As for safety assessment, liraglutide did not increase the incidence of hypoglycemia (OR = 0.75, 95% CI[0.32–1.77], P = 0.51) and gastrointestinal (OR = 1.15, 95% CI[0.72–1.85], P = 0.55) events. Consequently, liraglutide had favorable effects on blood glucose, cardiac function, lipid profile and an acceptable safety profile. [Display omitted] • Little is known about the cardioprotective effects of antidiabetic drugs. • Liraglutide significantly reduced blood glucose, improved lipid metabolism. • Liraglutide protected cardiac function in T2DM patients complicated with CAD. • Liraglutide prevented ventricular remodeling in T2DM patients complicated with CAD. • Liraglutide showed no increased risk in gastrointestinal and hypoglycemia events. [ABSTRACT FROM AUTHOR]