Association Between Prognostic Nutritional Index and Prognosis in Patients With Heart Failure: A Meta-Analysis.

Background: The prognostic nutritional index (PNI) has been proposed as a marker of malnutrition and associated with the prognosis of cardiovascular disease. However, whether PNI can serve as a potential biomarker for the prognosis of heart failure (HF) upon those established risk factors were still controversial. This meta-analysis aimed to generate comprehensive evidence on the prognostic value of PNI in patients with HF. Methods: Multiple databases (PubMed, Embase, the Cochrane Library, and Google Scholar) were searched for related studies up to January 31, 2022. Observational studies accessed associations between PNI levels and the prognosis in patients with HF were included for meta-analysis. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. Results: Fourteen studies, comprising 19,605 patients with HF were included for meta-analysis. The median follow-up duration was 18.5 months. Compared with those with higher PNI (normal nutritional status), patients with HF with lower PNI (malnourished) were associated with a higher risk of all-cause mortality (HR 1.53, 95% CI 1.27-1.85) and composite major adverse cardiac outcomes (MACEs; HR 2.26, 95% CI 1.54-3.31) in the multivariable-adjusted model. Furthermore, when PNI was defined as per 1 increment as a continuous metric, higher PNI was associated with a decrease in all-cause mortality (per 1 increment of PNI: HR 0.94, 95% CI 0.88-0.96) and MACEs (per 1 increment of PNI: HR 0.97, 95% CI 0.95-0.98). Conclusions: The PNI can serve as an easily calculated bedside "malnutrition-inflammation" biomarker in HF. Lower PNI was associated with a worse prognosis in patients with HF.

Modulation of miRNAs by vitamin C in H2O2­exposed human umbilical vein endothelial cells.

Vitamin C plays a protective role in oxidative damage by blocking the effects of free radicals. The present study investigated the mechanisms through which vitamin C partly mediates anti­apoptotic and antioxidant functions via the regulation of microRNAs (miRNAs or miRs). For this purpose, a global miRNA expression analysis on human umbilical vein endothelial cells (HUVECs) treated with vitamin C was conducted using microarrays containing human precursor and mature miRNA probes. The results revealed that there were 42 identical miRNAs among the differentially expressed miRNAs in the HUVEC group and H2O2 + vitamin C­treated HUVEC group compared to the H2O2­exposed HUVEC group, including 41 upregulated miRNAs and 1 down­regulated miRNA. Using bioinformatics analysis, differentially expressed miRNAs were investigated to identify novel target mRNAs and signaling pathways. Pathway enrichment analyses revealed that apoptosis, the mitogen­activated protein kinase (MAPK) signaling pathway, phosphoinositide 3­kinase (PI3K)/Akt signaling pathway and oxidative phosphorylation were significantly enriched. The results from western blot analysis demonstrated that the interleukin (IL)10, matrix metalloproteinase (MMP)2, cAMP­response element binding protein (CREB) and p­CREB protein expression levels in HUVECs transfected with hsa­miR­3928­5p and induced by H2O2 were significantly downregulated; the MAPK9, caspase­3 (CASP3) and p­CASP3 protein expression levels in HUVECs transfected with hsa­miR­323a­5p and induced by H2O2 were significantly downregulated. The present study therefore demonstrates that vitamin C partly exerts protective effects on HUVECs through the regulation of miRNA/mRNA axis expression.

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction.

Statin treatment reduces cardiovascular risk. However, individuals with well-controlled low-density lipoprotein (LDL) levels may remain at increased risk owing to persistent high triglycerides and low high-density lipoprotein cholesterol. Because resveratrol promotes glucose metabolism and mitigates cardiovascular disorders, we explored its mechanism of protective action on high-fat-induced endothelial dysfunction. Human umbilical venous endothelial cells were treated with oxidized LDL (ox-LDL) in vitro. Endothelial function, cell survival, proliferation, migration, and oxidative stress were analyzed through western blots, quantitative polymerase chain reaction, ELISA, and immunofluorescence. ox-LDL induced endothelial cell apoptosis, proliferation arrest, and mobilization inhibition, all of which resveratrol reduced. ox-LDL suppressed the activities of mitochondrial respiration complex I and III and reduced levels of intracellular antioxidative enzymes, resulting in reactive oxygen species overproduction and mitochondrial dysfunction. Resveratrol treatment upregulated Bnip3-related mitophagy and prevented ox-LDL-mediated mitochondrial respiration complexes inactivation, sustaining mitochondrial membrane potential and favoring endothelial cell survival. We found that resveratrol enhanced Bnip3 transcription through hypoxia-inducible factor 1 (HIF1) and 5' AMP-activated protein kinase (AMPK). Inhibition of AMPK and HIF1 abolished resveratrol-mediated protection of mitochondrial redox balance and endothelial viability. Together, these data demonstrate resveratrol reduces hyperlipemia-related endothelial damage by preserving mitochondrial homeostasis.

SERCA overexpression reduces reperfusion-mediated cardiac microvascular damage through inhibition of the calcium/MCU/mPTP/necroptosis signaling pathways.

Endothelial cells lining the microvasculature are particularly vulnerable to the deleterious effects of cardiac ischemia/reperfusion (I/R) injury, a susceptibility that is partially mediated by dysregulated intracellular calcium signals. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) functions to recycle calcium from the cytosol back to the endoplasmic reticulum. The purpose of this study is to explore the roles and mechanisms of SERCA in protecting microcirculation against cardiac I/R injury. Our data showed that overexpression of SERCA significantly reduced I/R-induced luminal stenosis and vascular wall edema, possibly through normalization of the ratio between eNOS and ET-1. I/R-induced erythrocyte morphological changes in micro-vessels could be reversed by SERCA overexpression through transcriptional inhibition of the expression of adhesive factors. In addition, SERCA-sustained endothelial barrier integrity reduced the likelihood of inflammatory cells infiltrating the myocardium. Furthermore, we found that SERCA overexpression attenuated intracellular calcium overload, suppressed mitochondrial calcium uniporter (MCU) expression, and prevented the abnormal opening of mitochondrial permeability transition pores (mPTP) in I/R-treated cardiac microvascular endothelial cells (CMECs). Interestingly, the administration of calcium activator or MCU agonist induced endothelial necroptosis in vitro and thus abolished the microvascular protection afforded by SERCA in reperfused heart tissue in vivo. In conclusion, by using gene delivery strategies to specifically target SERCA in vitro and in vivo, we identify a potential novel pathway by which SERCA overexpression protects microcirculation against cardiac I/R injury in a manner dependent on the calcium/MCU/necroptosis pathway. These findings should be taken into consideration in the development of pharmacological strategies for therapeutic interventions against cardiac microvascular I/R injury.

New dibenzodioxocinone and pyran-3,5-dione derivatives from the deep-sea-derived fungus Penicillium canescens SCSIO z053.

A new isopentylated dibenzodioxocinone, canescenin A (1), and a new isopentylated pyran-3,5-dione derivative, canescenin B (2), were isolated from an extract of the deep-sea-derived fungus Penicillium canescens SCSIO z053. Their structures were elucidated by spectroscopic analysis. It was rare to obtain pyran-3,5-dione derivatives from nature. Antibacterial, cytotoxic, and antiviral activities of 1 and 2 were also evaluated.

A subset of circulating microRNAs is expressed differently in patients with myocardial infarction.

The objective of the present study was to analyze the differences in the plasma microRNA (miRNA) expression profiles between patients with myocardial infarction (MI) (with or without heart failure) and individuals in a normal control group using an miRNA array. Specific miRNAs were selected to explore novel circulating markers for MI and heart failure. A total of 15 patients with heart failure and 10 patients without heart failure following acute MI (AMI) were recruited as the AMI with heart failure (AMHF) and with no heart failure (AMNHF) groups, respectively. In addition, 10 patients with an older (≥ 1 year) MI with heart failure were selected as the old MI and heart failure (OMHF) group. Finally, 10 patients with normal coronary angiograms were recruited as the control (N) group. The plasma of peripheral venous blood was collected for miRNA array detection. In the AMHF group, the expression of 17 miRNAs was upregulated and the expression of 21 miRNAs was downregulated by >1.5-fold compared with that in the AMNHF group. Compared with the N group, the expression of miRNAs in the AMNHF group was upregulated in 38 and downregulated in 48 cases by >1.5-fold. Compared with the OMHF group, 13 miRNAs were upregulated and 43 were downregulated by >1.5-fold in the AMHF group. Significant differences in the miRNA expression profiles were observed between patients with different stages of heart failure following MI and individuals in the normal control group. These differences were determined using miRNA array analysis methods based on the peripheral blood plasma. Thus, the specific miRNAs identified in this study may be novel circulating markers for MI and heart failure.

[Effect of different doses of perindopril on myocardial energy expenditure in patients with heart failure following myocardial infarction].

OBJECTIVE: To investigate the changes of myocardial energy expenditure in patients with heart failure following myocardial infarction after treatment with different doses of perindopril. METHODS: Sixty-three patients with heart failure after myocardial infarction were treated with perindopril for 12 months at the doses of 4 mg (group N) and 8 mg (group H). Doppler imaging was used to measure the structural and systolic functional parameters before and after the treatment, and the circumferential end-systolic wall stress (cESS) and myocardial energy expenditure (MEE) were calculated. The biochemical indicators including serum creatinine and plasma NT-proBNP were detected before and after the treatment. RESULTS: The two groups had similar measurements before treatment. After 12 months of perindopril treatment, the patients in group N showed higher LA, LV, RA, RV, LVIDs, AD, cESS, lgNT-proBNP, and MEE with lower LVFS and LVEF than those in group H. Compared to those before treatment, LVFS and LVEF were increased and LA, LV, RA, RV, AD, LVIDs, LVMI, lgNT-proBNP and MEEm lowered after the 12-month treatment in group H. Significant changes were also found in the measured parameters except for PWTs, LVET, LVSV and LVFS in group N after the treatment. Bivariate analysis showed a significant positive correlation between MEE and lgNT-proBNP (r=0.513, P<0.01). CONCLUSION: A 12-month treatment with perindopril can suppress myocardial remodeling, improve left ventricular systolic function, and lower NT-proBNP and myocardial energy expenditure in patients with heart failure after myocardial infarction, and a higher dose can produce better results.

[Application of ¹H-NMR-based pattern recognition in serum metabolomics of patients with chronic heart failure].

OBJECTIVE: To investigate the feasibility of applying (1)H-NMR-based pattern recognition in the studies of serum metabonomics in chronic heart failure (HF). METHODS: (1)H-NMR technique was applied for examination of the serum samples from 9 patients with chronic heart failure and 6 healthy individuals. The data were analyzed for pattern recognition through principal component analysis (PCA) and Orthogonal Partial Least Square (OPLS) to determine the differences in serum metabolites between the two groups. The recognition ability of the two analysis methods were compared. RESULTS: The serum (1)H-NMR spectra of heart failure patients and healthy individuals were significantly different. The PCA method failed to distinguish the patterns between the two groups, but OPLS clearly differentiated the two groups. CONCLUSIONS: (1)H-NMR technique is effective in the study of serum metabolomics in chronic heart failure. The serum metabonomics of patients with chronic heart failure and the healthy individuals are significantly different. OPLS pattern recognition method is superior to PCA method in that the former can remove the influence of non-experimental factors and provide an improved characterization.

[Effect of primary percutaneous coronary intervention on plasma B-type natriuretic peptide in patients with acute myocardial infarction].

OBJECTIVE: To observe the effect of primary percutaneous coronary intervention (PCI) on plasma B-type natriuretc peptide (BNP) in patients with acute myocardial infarction (AMI). METHODS: Thirty-eight patients with AMI were divided into two groups for PCI (n=26) and conventional treatment (n=12). The plasma BNP levels were measured by fluorescence immunoassay (FIA) in these patients immediately, 24 h, 7 d, and 30 days after admission, and the infarct-related coronary arteries (IRA) were treated only with emergency interventional therapy in PCI group. RESULTS: BNP of the patients in the PCI and conventional treatment group B increased immediately and 24 h after admission, but there was no significant difference between the two groups (243.74+/-75.68 vs 228.65+/-82.32 and 283.42+/-88.66 vs 275.48+/-89.67, P>0.05). BNP in PCI group decreased but that in conventional treatment group increased 7 days after admission, showing significant difference between them (203.63+/-59.42 vs 388.74+/-108.52, P<0.05 ). BNP remained significantly lower in the PCI group than in the other group 30 days after admission (96.31+/-43.22 vs 237.66+/-75.48, P<0.01). Emergency PCI for different IRA resulted in the significant difference in BNP between the patients, and intervention of the left anterior descending artery (LAD) resulted in more obvious BNP reduction in comparison with that due to interventional of the right coronary artery (RCA) and left circumflex coronary artery (LCX). The changes in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension (LVEDD) were correlated to the changes of BNP. The mean BNP in the 3 fatal cases was nearly 10-fold higher than the normal level. CONCLUSIONS: BNP of AMI patients decreases on days 7 and 30 after reperfusion therapy with primary PCI, and the reduction can be more obvious 30 days after admission.