Myocardial infarction (MI) is a coronary artery-related disease and ranks as the leading cause of sudden death globally. Resveratrol (Res) is a bioactive component and has presented antioxidant, anti-inflammatory and anti-microbial properties. However, the effect of Res on ferroptosis during MI progression remains elusive. Here, we aimed to explore the function of Res in the regulation of ferroptosis and myocardial injury in MI. We observed that the treatment of Res attenuated the MI-related myocardium injury and fibrosis in the rats. The expression of collagen 1 and α-SMA was induced in MI rats, in which the treatment of Res could decrease the expression. Treatment of Res suppressed the levels of IL-6 and IL-1β in MI rats. The GSH levels were inhibited and MDA, lipid ROS, and Fe2+ levels were induced in MI rats, in which the treatment of Res could reverse the phenotypes. Meanwhile, the expression of GPX4 and SLC7A11 was reduced in MI rats, while the treatment of Res could rescue the expression in the model. Meanwhile, Res relieved oxygen-glucose deprivation (OGD)-induced cardiomyocyte injury. Importantly, Res repressed OGD-induced cardiomyocyte ferroptosis in vitro. Mechanically, we identified that Res was able to enhance GPX4 expression by inducing KAT5 expression. We confirmed that KAT5 alleviated OGD-induced cardiomyocyte injury and ferroptosis. The depletion of KAT5 or GPX4 could reverse the effect of Res on OGD-induced cardiomyocyte injury. Thus, we concluded that Res attenuated myocardial injury by inhibiting ferroptosis via inducing KAT5/GPX4 in myocardial infarction. Our finding provides new evidence of the potential therapeutic effect of Res on MI by targeting ferroptosis.

To study the effect of novel bioresorbable scaffold composed of poly-L-lactic acid (PLLA) and amorphous calcium phosphate (ACP) nanoparticles on inflammation and calcification of surrounding tissues after implantation. Ninety six PLLA/ACP scaffolds and 96 PLLA scaffolds were randomly implanted in the back muscle tissue of 48 SD rats. At the 1st, 2nd, 4th, and 12th weeks after implantation, the calcium, phosphorus, and alkaline phosphatase levels in the blood serum and the contents of calcium and alkaline phosphatase in the tissue surrounding the scaffolds were measured. Hematoxylin-eosin staining was performed to count the inflammatory cells. Von kossa staining was performed to observe calcification of the surrounding tissue around the scaffold. NF-κB staining was performed by immunohistochemistry to calculate the positive expression index of inflammatory cells. Western blot was used to detect the expression of IL-6 and BMP-2 in the tissues surrounding the scaffolds. At the 1st, 2nd, 4th, and 12th weeks after scaffold implantation, there were no significant difference in the serum concentration of calcium, phosphorus, alkaline phosphatase and in the tissue homogenate concentration of alkaline phosphatase between the two groups (P > 0.05). The level of calcium in tissue homogenates was lower in the PLLA/ACP group than in the PLLA group at 12-week (P < 0.05). The hematoxylin-eosin staining results showed that the inflammatory cell count in the PLLA/ACP group was lower than the PLLA group at 4-week and 12-week (P < 0.05). The results of NF-kB positive expression index showed that the PLLA group was significantly more than the PLLA/ACP group at 4-week and 12-week (P < 0.01). Western blot results showed that IL-6 expression levels in the PLLA/ACP group scaffolds were significantly lower than those in the control group at the 2-week, 4-week and 12-week (P < 0.05). The expression of BMP-2 in the PLLA group was significantly lower than that in the control group at 4-week and 12-week (P < 0.05). The PLLA/ACP composite material has good histocompatibility. The integration of nanoscale ACPs reduces the inflammatory response induced by acidic metabolites of PLLA material and may inhibit tissue calcification by reducing the amount of calcification factors in the body.

Purpose. Our previous research has confirmed that the addition of nano-amorphous calcium phosphate (ACP) materials can improve the support of poly-L-lactic acid (PLLA) vascular scaffolds. Based on this, we continued to explore the effect of novel bioresorbable scaffold composed of PLLA and ACP nanoparticles on inflammation and calcification of surrounding tissues after scaffold implantation in porcine coronary artery. Methods. PLLA/ACP scaffolds in the experimental group and PLLA scaffolds in the control group were implanted into the coronary arteries of small pigs. Serum levels of C-reactive protein (CRP), calcium (Ca), and alkaline phosphatase (ALP) were measured before implantation and at 1, 6, 12, and 24 months after operation. Intravascular ultrasonography (IVUS) was performed to evaluate the vascular calcification score. The scaffold and surrounding tissues were hematoxylin-eosin staining for inflammation score. The scaffold and surrounding tissues were stained with NF-κB and ALP, and the positive expression index was calculated. Western blot was used to detect the expression of IL-6 and BMP-2 in the tissues around the scaffold. Results. There was no statistically significant difference between the two groups in CRP, calcium, and ALP at preimplant, 1 month, 6 months, 12 months, and 24 months ( P > 0.05 ). The inflammation score, NF-κB positive expression index, and calcification score in the PLLA/ACP group were lower than that in the PLLA group at 12 months and 24 months ( P < 0   05 ). The ALP positive expression index in the PLLA/ACP group was lower than that in the PLLA group at 6 months, 12 months, and 24 months ( P < 0   05 ). Western blot results showed that the IL-6 expression level in the PLLA/ACP group was significantly lower than that in the control group at 6 months, 12 months, and 24 months ( P < 0.05 ). The expression of BMP-2 in the PLLA/ACP group was significantly lower than that in the control group at 12 months and 24 months ( P < 0.05 ). Conclusion. The PLLA/ACP composite scaffold has good biocompatibility. The incorporation of nanoscale ACP can reduce the inflammatory response caused by the acid metabolites of PLLA scaffolds, reduce the expression of procalcification factors in the body, and inhibit tissue calcification. The PLLA/ACP composite scaffold provides reliable guidance for the application and development of degradable vascular scaffold.

Background. Excessive myocardial oxidative stress could lead to the congestive heart failure. NADPH oxidase is involved in the pathological process of left ventricular (LV) remodeling and dysfunction. β3-Adrenergic receptor (AR) could regulate cardiac dysfunction proved by recent researches. The molecular mechanism of β3-AR regulating oxidative stress, especially NADPH oxidase, remains to be determined. Methods. Cardiac hypertrophy was constructed by the transverse aortic constriction (TAC) model. ROS and NADPH oxidase subunits expression were assessed after β3-AR agonist (BRL) or inhibitor (SR) administration in cardiac hypertrophy. Moreover, the cardiac function, fibrosis, heart size, oxidative stress, and cardiomyocytes apoptosis were also detected. Results. β3-AR activation significantly alleviated cardiac hypertrophy and remodeling in pressure-overloaded mice. β3-AR stimulation also improved heart function and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis. Meanwhile, β3-AR stimulation inhibited superoxide anion production and decreased NADPH oxidase activity. Furthermore, BRL treatment increased the neuronal NOS (nNOS) expression in cardiac hypertrophy. Conclusion. β3-AR stimulation alleviated cardiac dysfunction and reduced cardiomyocytes apoptosis, oxidative stress, and fibrosis by inhibiting NADPH oxidases. In addition, the protective effect of β3-AR is largely attributed to nNOS activation in cardiac hypertrophy.

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