Oral iron supplementation in patients with heart failure: a systematic review and meta-analysis.

AIMS: This review aimed to assess whether oral iron supplementation in a chronic heart failure (HF) population with iron deficiency (ID) or mild anaemia is safe and effective according to evidence-based medicine. METHODS: We retrieved 1803 records from the PubMed, Embase, and the Cochrane Library databases from 1 January 1991 to 15 September 2021. The clinical outcome of oral iron supplementation for ID anaemia in patients with HF was the primary endpoint. The primary safety measures included adverse events and all-cause mortality, and efficacy measures included transferrin saturation (Tsat), ferritin levels, and the 6-min walk test (6MWT). The rate ratio (RR) was used to pool the efficacy measures. RESULTS: Five randomized controlled trials that compared oral iron treatment for patients with the placebo group and included a combined total of 590 participants were analysed. No significant difference was found in all-cause death between oral iron treatment and placebo groups (RR = 0.77; 95% confidence intervals (CI), 0.46-1.29, Z = 0.98; P = 0.33). However, adverse events were not significantly higher in the iron treatment group (RR = 0.83; 95% CI, 0.60-1.16, Z = 1.07; P = 0.28). In addition, ferritin levels and Tsat were slightly increased after iron complex administration in patients with HF but were not statistically significant (ferritin: mean difference [MD] = 2.70, 95% CI, -2.41 to 7.81, Z = 1.04; P = 0.30; Tsat: MD = 27.42, 95% CI, -4.93 to 59.78, Z = 1.66; P = 0.10). No significant difference was found in exercise capacity, as indicated by the 6MWT results (MD = 59.60, 95% CI, -17.89 to 137.08, Z = 1.51; P = 0.13). We also analysed two non-randomized controlled trials with follow-up results showing that oral iron supplementation increased serum iron levels (MD = 28.87, 95% CI, 1.62-56.12, Z = 2.08; P = 0.04). CONCLUSIONS: Based on the current findings, oral iron supplementation can increase serum iron levels in patients with HF and ID or mild anaemia but does not improve Tsat and 6MWT. In addition, oral iron supplementation is relatively safe.

MCC950 ameliorates ventricular arrhythmia vulnerability induced by heart failure.

MCC950, a specific NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inhibitor, has been reported to play a role in various cardiovascular diseases. However, its role in heart failure (HF)-induced ventricular arrhythmias (VAs) remains unclear. Hence, the present study aimed to clarify the role and underlying mechanisms of MCC950 in HF-induced VAs. Male C57BL/6 mice were induced with HF via transverse aortic constriction (TAC). Histological analysis, echocardiography, electrophysiological investigation, and western blot analysis were conducted to evaluate VA vulnerability induced by TAC and the potential mechanisms underlying the effects. MCC950 markedly improved cardiac function and decreased pulmonary edema induced by HF. Moreover, MCC950 also decreased VA vulnerability, as shown by the shortened QTc duration and action potential duration 90 (APD90), reduced APD alternans threshold, and decreased VA induction rate. Furthermore, MCC950 treatment significantly reversed TAC-induced cardiac hypertrophy and fibrosis. In addition, MCC950 administration increased the protein levels of ion channels (Kv4.2, KChIP2, and Cav1.2). Mechanistically, the above changes induced by MCC950 were due to the inhibition of the NLRP3 inflammasome. As a specific NLRP3 inhibitor, MCC950 significantly decreased HF-induced VA vulnerability by reversing cardiac structural remodeling and electrical remodeling, and the mechanism through which MCC950 exhibited this effect was inhibition of NLRP3 inflammasome activation.

Galectin-1 alleviates myocardial ischemia-reperfusion injury by reducing the inflammation and apoptosis of cardiomyocytes.

Myocardial ischemia-reperfusion injury (MIRI) is one of the leading causes of morbidity and mortality worldwide, for which there is no effective treatment. The present study aimed to assess novel methods of clinical MIRI treatment by studying the effects of galectin-1 (Gal-1) on MIRI. Male 2-month-old Sprague Dawley rats and the rat cardiomyocyte cell line H9c2 were utilized in the present study. A rat model of MIRI was constructed by ligating the left anterior descending coronary artery, which was subsequently treated with Gal-1. Differences in myocardial injury were then assessed by hematoxylin and eosin (H&E) staining. In addition, the levels of inflammation and apoptosis in rat myocardial tissue were determined by immunohistochemistry staining. Hypoxia-reoxygenation was used to construct a model of MIRI in H9c2 cells. The effect of Gal-1 on the apoptosis and viability of H9c2 cells was also verified by flow cytometry and a Cell Counting Kit-8 assay. The results of H&E staining revealed that Gal-1 alleviated MIRI. Echocardiography demonstrated that Gal-1 improved cardiac function in rats following MIRI. In addition, MIRI increased levels of inflammation and apoptosis in rat myocardial tissues, with Gal-1 treatment reversing this effect. In cellular experiments, Gal-1 served anti-inflammatory and anti-apoptotic effects in hypoxic/reoxygenated cardiomyocytes. In conclusion, Gal-1 served a significant protective effect on the myocardial tissue after ischemia-reperfusion by reducing the level of inflammation and apoptosis in cardiomyocytes.

LncRNA MHRT Promotes Cardiac Fibrosis via miR-3185 Pathway Following Myocardial Infarction.

Long-chain noncoding RNA (lncRNA) is a new class of molecular regulators in heart development and disease. However, the role of specific lncRNA in cardiac fibrosis remains to be fully explored. This study aimed to investigate the role and potential mechanism of lncRNA MHRT in myocardial fibrosis after myocardial infarction (MI).Cardiac fibroblasts (CFs) were isolated from a mouse model of MI. The expression levels of MHRT and miR-3185 in the hearts of MI and CFs mice treated with transforming growth factor beta 1 (TGF-ß1) were analyzed by qRT-PCR. The collagen expression was assessed using qRT-PCR and Western blot. Cell proliferation was assessed by performing MTT and EdU assays. The direct interaction between lncRNA and miRNA was analyzed by luciferase assay, RNA-binding protein immunoprecipitation (RIP) assay, and RNA pull-down assay.The expression levels of MHRT were raised in MI and CFs mice treated with TGF-ß1. Overexpression of MHRT promoted collagen production and CF proliferation, while silencing of MHRT showed the opposite effect. MiR-3185 was a target gene of MHRT. In addition, overexpression of MHRT reduced the expression levels of miR-3185, and siMHRT reversed the inhibitory effect of TGF-ß1 on the expression of miR-3185. Overexpression of miR-3185 inhibited the upregulation of Col I and Col III induced by TGF-ß1.MHRT promoted cardiac fibrosis after MI through miR-3185 and increased myocardial collagen deposition and promoted myocardial fibrosis.

The GLP-1 receptor agonist liraglutide protects against oxidized LDL-induced endothelial inflammation and dysfunction via KLF2.

Cardiovascular complications are the major causes of the mortality and morbidities in diabetic patients. The diabetic patients have an increased risk of developing atherosclerosis, which could lead to heart attack and stroke. Glucagon-like peptide 1 (GLP-1) receptor agonists are a class of potent anti-glycemic agents to treat diabetes. Recently, several GLP-1 receptor agonists have been found to have cardiovascular benefit independent of their glucose lowing ability. Liraglutide is one of clinically approved effective GLP-1 receptor agonists. In this study, we explored the molecular mechanism of Liraglutide against oxidized low-density lipoprotein (ox-LDL) in cultured endothelial cells. Our data show that Liraglutide treatment ameliorates ox-LDL caused reduction of the transcriptional factor KLF2. In the same experiment, Liraglutide also rescues ox-LDL induced reduction of mitogen-activated protein kinase (MAPK) kinase extracellular signal regulated kinase 5 (ERK5) phosphorylation, and blockage of ERK5 activity by its inhibitor XMD8-92 abolishes the protection of Liraglutide on KLF2 expression. These facts suggest that the action of Liraglutide on endothelial KLF2 is dependent on ERK5. Liraglutide also recovers ox-LDL caused reduction of endothelial tight junctions protein Occludin and ameliorates ox-LDL induced endothelial monolayer permeability increase. On the other hand, Liraglutide inhibits ox-LDL induced expression of vascular adhesion molecules (E-selectin and vascular cell adhesion molecule 1), and prevents ox-LDL induced attachment of monocytes adhesion to endothelial cells. Moreover, Liraglutide mitigates ox-LDL triggered reduction of endothelial nitric oxide synthase (eNOS) expression and NO release. Collectively, our study provides multiple facets of the mechanisms that Liraglutide is a protective agent in endothelial cells and has the potential implication in therapeutic usage of vascular complication in diabetes patients. © 2019 IUBMB Life, 71(9):1347-1354, 2019.