Acute myocardial infarction (MI) triggers oxidative stress, which worsen cardiac function, eventually leads to remodeling and heart failure. Unfortunately, effective therapeutic approaches are lacking. Fibroblast growth factor 7 (FGF7) is proved with respect to its proliferative effects and high expression level during embryonic heart development. However, the regulatory role of FGF7 in cardiovascular disease, especially MI, remains unclear. FGF7 expression was significantly decreased in a mouse model at 7 days after MI. Further experiments suggested that FGF7 alleviated MI-induced cell apoptosis and improved cardiac function. Mechanistic studies revealed that FGF7 attenuated MI by inhibiting oxidative stress. Overexpression of FGF7 actives nuclear factor erythroid 2-related factor 2 (Nrf2) and scavenging of reactive oxygen species (ROS), and thereby improved oxidative stress, mainly controlled by the phosphatidylinositol-3-kinase α (PI3Kα)/AKT signaling pathway. The effects of FGF7 were partly abrogated in Nrf2 deficiency mice. In addition, overexpression of FGF7 promoted hexokinase2 (HXK2) and mitochondrial membrane translocation and suppressed mitochondrial superoxide production to decrease oxidative stress. The role of HXK2 in FGF7-mediated improvement of mitochondrial superoxide production and protection against MI was verified using a HXK2 inhibitor (3-BrPA) and a HXKII VDAC binding domain (HXK2VBD) peptide, which competitively inhibits localization of HXK2 on mitochondria. Furthermore, inhibition of PI3Kα/AKT signaling abolished regulation of Nrf2 and HXK2 by FGF7 upon MI. Together, these results indicate that the cardio protection of FGF7 under MI injury is mostly attributable to its role in maintaining redox homeostasis via Nrf2 and HXK2, which is mediated by PI3Kα/AKT signaling.

Objectives: The purpose of this study was to investigate the independent effect of the ratio of red blood cell distribution width (RDW) to albumin (RA) on all-cause mortality in patients after percutaneous coronary intervention (PCI).Methods: Clinical data were obtained from the Multiparameter Intelligent Monitoring in Intensive Care-III (MIMIC-III) database version 1.4 and the database of Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University. We used the MIMIC-III database for model training, and data collected from the Second Affiliated Hospital of Wenzhou Medical University for validation. The primary outcome of our study was 90-day mortality. Cox proportional hazards regression model was used to estimate hazard ratio (HR) for the association between RA and all-cause mortality in patients after PCI. Pearson correlation analysis was conducted to assess the relationship between RA and Gensini score or cardiac troponin I (cTnI).Results: A total of 707 patients were eligible in MIMIC-III database, including 432 males, with a mean age of 70.29 years. For 90-day all-cause mortality, in the adjusted multivariable model, the adjusted HRs [95% confidence intervals (CIs)] for the second (RA: 3.7–4.5 ml/g) and third (RA >4.5 ml/g) tertiles were 2.27 (1.11, 4.64) and 3.67 (1.82, 7.40), respectively, compared to the reference group (RA <3.7 ml/g) (p < 0.05). A similar relationship was also observed for 30-day all-cause mortality and 1-year all-cause mortality. No significant interaction was observed in subgroup analysis. Receiver operating characteristic (ROC) curve analysis proved that the ability of RA to predict the 90-day mortality was better than that of RDW or albumin alone. The correlation coefficient between Gensini score and RA was 0.254, and that between cTnI and RA was 0.323.Conclusion: RA is an independent risk factor for all-cause mortality in patients after PCI. The higher the RA, the higher the mortality. RA has a good predictive ability for all-cause mortality in patients after PCI, which is better than RDW or albumin alone. RA may be positively correlated with the severity of coronary artery disease (CAD) in patients with CAD.

Cardiac hypertrophy occurs initially in response to an increased cardiac load as a compensatory mechanism to maintain cardiac output. However, sustained pathological hypertrophy can develop into heart failure and cause sudden death. Fibroblast growth factor 20 (FGF20) is a member of the fibroblast growth factor family, which involved in apoptosis, aging, inflammation, and autophagy. The precise function of FGF20 in pathological cardiac hypertrophy is unclear. In this study, we demonstrated that FGF20 was significantly decreased in response to hypertrophic stimulation. In contrast, overexpression of FGF20 protected against pressure overload-induced cardiac hypertrophy. Mechanistically, we found that FGF20 upregulates SIRT1 expression, causing deacetylation of FOXO1; this effect promotes the transcription of downstream antioxidant genes, thus inhibits oxidative stress. In content, the anti-hypertrophic effect of FGF20 was largely counteracted in SIRT1-knockout mice, accompanied by an increase in oxidative stress. In summary, our findings reveal a previously unknown protective effect of FGF20 on pathological cardiac hypertrophy by reducing oxidative stress through activation of the SIRT1 signaling pathway. FGF20 is a potential novel molecular target for preventing and treating pressure overload-induced myocardial injury.

Objectives: Myocardial infarction (MI) commonly occurs in patients with coronary artery disease and have high mortality. Current clinical strategies for MI still limited to reducing the death of myocardial cells but failed to replace these cells. This study aimed to investigate the role of fibroblast growth factor 6 (FGF6) in enhancing the proliferative potential of cardiomyocytes (CMs) after ischemic injury via the Hippo pathway.Materials and Methods: Expression of FGF6 protein was analysed in mice with MI induced by ligation of the left anterior descending coronary artery. Activation of the Hippo pathway and the proliferation potential were examined in ischemic CMs, treated with FGF6 protein or transfected with an adeno‐virus carrying FGF6 sh‐RNA. Immunofluorescence staining and western blotting were performed to assess the relationship between FGF6 and the Hippo pathway.Results: We found that FGF6 expression was significantly increased in the MI mouse model. Knockdown of FGF6 synthesis resulted in poorer heart function after MI. By contrast, treatment with recombinant human FGF6 protein improved heart function, reduced infarct size, and promoted cardiac repair. Additionally, FGF6 restrains the activation of the Hippo pathway and subsequently promotes nuclear accumulation of YAP. This was largely counteracted by treatment with extracellular signal‐regulated kinase 1/2 (ERK1/2) inhibitor U0126.Conclusion: FGF6 inhibits the Hippo pathway via ERK1/2, and facilitates nuclear translocation of YAP, and thereby promotes cardiac repair after MI.

Background and Purpose. Docosahexaenoic acid (DHA) is a type of polyunsaturated fatty acid enriched in cod liver oil and seaweed. It is necessary for the human body and has important functions, such as antioxidation and antiatherosclerosis activities. Long‐term oral administration of DHA or the use of DHA at the initial stage of ischemia can increase the level of autophagy and exert a protective effect on neurological functions related to cerebral infarction. However, the effect of DHA on myocardial injury and cardiac insufficiency after myocardial infarction (MI) is unknown. This study was aimed at exploring whether DHA plays a protective role in AMI and its specific molecular mechanism. Experimental Method. In vitro cardiomyocyte hypoxia and in vivo MI injury models were used to determine the role of DHA in MI. Hypoxic injury induced damage in cultured neonatal mouse cardiomyocytes (NMCs). The C57BL/6J mouse MI model was established by permanent ligation of the left anterior descending branch. Main Results. DHA improved the cardiomyocyte viability of NMCs induced by hypoxia injury and reduced cell necrosis. DHA reduced infarct size, improved heart function, and reduced the degree of myocardial fibrosis in mice after MI. In addition, DHA enhanced autophagy flux and reduced apoptosis in vitro and in vivo. In addition, we found that chloroquine, an autophagy inhibitor, blocked the protective effect of DHA on cardiomyocyte apoptosis and cardiac dysfunction, indicating that DHA exerts cardioprotective effects in part by promoting autophagy flux. We also observed that DHA enhanced autophagy flux by activating the AMPK/mTOR signaling pathway. Conclusions and Significance. In conclusion, our findings indicate for the first time that DHA improves MI‐induced cardiac dysfunction by promoting AMPK/mTOR‐mediated autophagic flux.