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Coronary microembolization (CME) caused by physical obstruction in coronary microcirculation induces myocardial apoptosis and cardiac dysfunction, and it was reported that the inactivation of the Nrf2/HO-1 signaling was involved in this process. Astaxanthin (AST) is a reddish pigment that belongs to keto-carotenoids. It is also a potent antioxidant and has been reported to activate Nrf2/HO-1 signaling in vein endothelial cells. However, it is still unknown whether AST is able to activate Nrf2/HO-1 signaling pathway to protect cardiac functions from CME in vivo. To address this question, rats were orally administrated with AST or AST plus Zinc protoporphyrin IX (ZnPP, a HO-1 inhibitor), followed by CME modeling operation. Then, cardiac function was evaluated by echocardiographic measurement. Myocardial infarction was measured by HBFP staining, and apoptosis was assessed by TUNEL staining. The protein levels and mRNA expressions of Bax and Bcl-2 were measured by Western blot and qRT-PCR, respectively. ELISA was performed to measure the activity of enzymes related to oxidative stress. AST pretreatment dramatically attenuated CME-induced cardiac dysfunction, myocardial infarction, and cardiomyocyte apoptosis. Mechanistically, AST suppressed CME-induced oxidative stress by re-activating Nrf2/HO-1 signaling. HO-1 inhibitor ZnPP completely eliminated the benefits of AST in CEM, supporting the critical role of Nrf2/HO-1 signaling in mediating the cardioprotective function of AST in CME. Conclusion: AST suppresses oxidative stress via activating Nrf2/HO-1 pathway and thus prevents CME-induced cardiomyocyte apoptosis and ameliorates cardiac dysfunction in rats.

Notch3 and TGF-β1 signaling play a key role in the pathogenesis and progression of chronic cardiovascular disease. However, whether Notch3 protects against myocardial infarction (MI) and the underlying mechanisms remains unknown. C57BL/6 mice were randomized to be treated with Notch3 siRNA (siNotch3) or lentivirus carrying Notch3 cDNA (Notch3) before coronary artery ligation. Four weeks after constructing MI model, cardiac function and fibrosis were compared between groups. The cardiac fibroblast cells (CFs) were isolated from newborn C57BL/6 mice (1-3 days old) and transfected with lentivirus carrying Notch3 cDNA. TGF-β1 (5 ng/ml), a well-known pro-fibrotic factor, was administered 72 h after Notch3 cDNA administration in CFs. The related proteins of fibrosis such as a-smooth muscle actin (a-SMA), Type I collagen, metalloprotease (MMP)-9 and the tissue inhibitor of metalloproteinases (TIMP)-2 were examined by western blot analysis. Notch3 cDNA treatment attenuated cardiac damage and inhibited fibrosis in mice with MI. Meanwhile, Notch3 siRNA administration aggravated cardiac function damage and markedly enhanced cardiac fibrosis in mice with MI. Overexpression of Notch3 inhibited TGF-β1-induced fibroblast-myofibroblast transition of mouse cardiac fibroblast cells, as evidenced by down-regulating a-SMA and Type I collagen expression. Notch3 cDNA treatment also increased MMP-9 expression and decreased TIMP-2 expression in the TGF-β1-stimulated cells. This study indicates that Notch3 is an important protective factor for cardiac fibrosis in a MI model, and the protective effect of Notch3 is attributable to its action on TGF-β1/Smad3 signaling.

The article titled "Retraction Note: Astaxanthin ameliorates cardiomyocyte apoptosis after coronary microembolization by inhibiting oxidative stress via Nrf2/HO-1 pathway in rats" has been retracted by the Editor-in-Chief of Naunyn-Schmiedeberg's Archives of Pharmacology. The retraction was made at the request of the corresponding author due to concerns about the high similarity of some images with previously published articles. The authors also admitted that some of the data were presented incorrectly, which undermines the conclusions of the article. The publisher, Springer Nature, remains neutral in this matter. [Extracted from the article]

Myocardial ischemia-reperfusion (IR) injury is associated with high disability and mortality worldwide. This study was to explore the roles of dioscin in the myocardial IR rats and discover the related molecular mechanisms. Rats were divided into 5 groups: sham, IR, IR + 15 mg/kg dioscin, IR + 30 mg/kg dioscin, and IR + 60 mg/kg dioscin. Heart rate (HR), mean arterial blood pressure (MAP), and rate pressure product (RPP) were evaluated at 10 minutes before ischemia, immediately after ischemia, and at the beginning, middle, and end of reperfusion. Arrhythmia score and myocardial infarct size were examined in rats of all groups. The serum creatine kinase-muscle/brain (CKMB) and cardiac troponin I (cTnI) levels were analyzed via enzyme-linked immunosorbent assay. Protein amount of total connexin 43 (T-Cx43) and phosphorylated connexin 43 (P-Cx43) was evaluated by Western blot. Ischemia reperfusion significantly decreased HR, MAP, and RPP of rats compared to the sham group. However, dioscin significantly attenuated the above phenomena in a dose-dependent manner. Dioscin markedly inhibited IR-induced increase in arrhythmias score, infarct size, and serum CKMB and cTnI levels. In addition, dioscin strikingly induced IR-repressed expression of T-Cx43 and P-Cx43. Our results suggested that dioscin pretreatment exhibited protective effects against myocardial IR injury. Moreover, we found that dioscin attenuated myocardial IR-induced ventricular arrhythmias via upregulating Cx43 expression and activation. [ABSTRACT FROM AUTHOR]