Background. Our previous study demonstrated that the expression of miR-16 was downregulated in the cell and animal models of atherosclerosis (AS), a main contributor to coronary artery disease (CAD). Overexpression of miR-16 inhibited the formation of foam cells by exerting anti-inflammatory roles. These findings indicated miR-16 may be an anti-atherogenic and CAD miRNA. The goal of this study was to further validate the expression of miR-16 in CAD patients and explore its therapeutic roles in an AS animal model. Methods. A total of 40 CAD patients and 40 non-CAD people were prospectively registered in our study. The AS model was established in ApoE-/- mice fed a high-fat diet. The model mice were randomly treated with miR-16 agomiR (n=10) or miR-negative control (n=10). Hematoxylin-eosin staining was conducted for histopathological examination in thoracic aorta samples. ELISA and immunohistochemistry were performed to determine the expression levels of inflammatory factors (IL-6, TNF-α, MCP-1, IL-1β, IL-10, and TGF-β). qRT-PCR and western blotting were carried out to detect the mRNA and protein expression levels of PDCD4, miR-16, and mitogen-activated protein kinase pathway-related genes. Results. Compared with the normal control, miR-16 was downregulated in the plasma and peripheral blood mononuclear cell of CAD patients, and its expression level was negatively associated with IL-6 and the severity of CAD evaluated by the Gensini score, but positively related with IL-10. Injection of miR-16 agomiR in ApoE-/- mice reduced the formation of atherosclerotic plaque and suppressed the accumulation of proinflammatory factors (IL-6, TNF-α, MCP-1, and IL-1β) in the plasma and tissues but promoted the secretion of anti-inflammatory factors (IL-10 and TGF-β). Mechanism analysis showed overexpression of miR-16 might downregulate target mRNA PDCD4 and then activate p38 and ERK1/2, but inactivate the JNK pathway. Conclusions. Our findings suggest miR-16 may be a potential diagnostic biomarker and therapeutic target for atherosclerotic CAD.

Purpose: Trimethylamine N-oxide (TMAO) is recently the main risk factor for coronary heart disease (CHD). Plasma lipid levels are conventionally used to predict coronary risk, but the correlation between TMAO and plasma lipid levels in unstable angina pectoris (UAP) was unclear. Our objective was to compare the plasma level of TMAO to lipoprotein ratios and conventional lipid parameters in UAP patients. Methods: A total of 114 control participants and 184 UAP patients were enrolled. Demographic characteristics were collected. Plasma levels of TMAO and lipid in all patients were measured and analyzed. The receiver operating characteristic analysis (ROC), univariate, and multivariate logistic regression analyses were carried out to examine the relationship between TMAO, lipoprotein ratios, conventional lipid parameters, and UAP. Results: The plasma levels of TMAO were remarkably increased in UAP patients (3.28 ± 1.97 µM) compared with control participants (1.52 ± 0.59 µM, P < 0.01). TMAO was significantly correlated with lipid levels in UAP patients. The ROC, univariate and multivariate logistic regression analysis both showed that the TMAO significantly increased the risk for occurrence of UAP. Conclusions: Our data indicate that the TMAO is superior to lipoprotein ratios and conventional lipid parameters in predicting occurrence of UAP.

Heart failure with preserved ejection fraction (HFpEF) accounts for almost half of all heart failure (HF) cases worldwide. Unfortunately, its incidence is expected to continue to rise, and effective therapy to improve clinical outcomes is lacking. Numerous efforts currently directed towards the pathophysiology of human HFpEF are uncovering signal transduction pathways and novel therapeutic targets. The nitric oxide-cyclic guanosine phosphate-protein kinase G (NO-cGMP-PKG) axis has been described as an important regulator of cardiac function. Suppression of the NO-cGMP-PKG signalling pathway is involved in the progression of HFpEF. Therefore, the NO-cGMP-PKG signalling pathway is a potential therapeutic target for HFpEF. In this review, we aim to explore the mechanism of NO-cGMP-PKG in the progression of HFpEF and to summarize potential therapeutic drugs that target this signalling pathway.

No abstract

Background Our previous study had found that the abundance of Lactobacillaceae in stool of acute coronary syndrome patients was significantly decreased. Experiments have confirmed that Lactobacillus has the effects of anti-inflammation, regulating blood lipids and improving cardiac injury after myocardial infarction. Purpose To explore the relationship between Lactobacillus and prognosis of acute myocardial infarction (AMI) patients treated by percutaneous coronary intervention (PCI) and its possible mechanism. Methods Patients with AMI who received emergency PCI from July 2017 to December 2018 in department of CCU were enrolled.Stool and blood samples were collected from all patients. The fecal 16S rDNA gene sequencing data from subjects were analyzed and subjects were categorized into Low, Medium and High level groups according to stool Lactobacillus measurements. The primary endpoints were major adverse cardiac events (MACE). Univariate and multivariate Cox regression were used to analyze the relationship between Lactobacillus and prognosis. Kaplan-Meier survival curve was used to characterize the association between the risk of MACE and Lactobacillus levels. Spearman correlation analysis and trend test were used to assess the relationship between Lactobacillus and Clinical index. Results A total of 254 patients were included in the analysis. The age was 65.90±11.56 years old,and 152 (59.84%) were male. The follow-up time was 652 (548.25, 753) days. Multivariate Cox regression showed that patients with Lactobacillus >7.1 copies/g presented lower risk of MACE (HR=0.179, 95% CI 0.076–0.422, P<0.001), compared to patients with Lactobacillus ≤3.6 copies/g.This difference was statistically significant in STEMI (HR=0.210, 95% CI 0.082–0.542, P=0.001). Subgroup analysis indicated that Lactobacillus was a protective factor,whereas the value was more evident for male smokers over 60 years old and whose BNP over 1000 pg/mL.Spearman correlation analysis showed that Lactobacillus was negatively correlated with WBC, NEUT, hs-CRP, TNT, CK, CK-MB and BNP, while positively correlated with LVEF. With the increasing of Lactobacillus, WBC, NEUT, hs-CRP, TNT, CK, CK-MB and BNP showed a downward trend, while LVEF had an upward trend. Conclusion Lactobacillus can significantly reduce the risk of MACE in STEMI patients treated by PCI, especially for male smokers over 60 years old. The underlying mechanism may be related to the fact that Lactobacillus can reduce inflammatory reaction, lessen cardiac injury and improve cardiac function. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): the Key Project of Scientific and Technological Support Plan of Tianjin in 2020 Correlation analysis between Lactobacill Subgroup analysis in different patients