Research development on gut microbiota and vulnerable atherosclerotic plaque.

The relationship between gut microbiota and its metabolites with cardiovascular disease (CVD) has been proven. In this review, we aim to conclude the potential mechanism of gut microbiota and its metabolites on inducing the formation of vulnerable atherosclerotic plaque, and to discuss the effect of intestinal metabolites, including trimethylamine-N-oxide (TMAO), lipopolysaccharide (LPS), phenylacetylglutamine (PAG), short-chain fatty acids (SCFAs) on plaque stability. Finally, we include the impact of gut microbiota and its metabolites on plaque stability, to propose a new therapeutic direction for coronary heart disease. Gut microbiota regulation intervenes the progress of arteriosclerosis, especially on coronary atherosclerosis, by avoiding or reducing the formation of vulnerable plaque, to lower the morbidity rate of myocardial infarction.

A new risk score for the assessment of outcomes for Chinese patients with peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a potentially life-threatening complication of pregnancy, but identifying patients at higher risk of this condition remains difficult. OBJECTIVES: We conducted a study to identify new risk factors associated with PPCM and predictors of poor outcomes. METHODS: This retrospective analysis included a total of 44 women with PPCM. As a control group, 79 women who gave birth around the same time as the PPCM patients and who did not have organic disease were included. A multivariate regression analysis was conducted to identify risk factors associated with PPCM and with delayed recovery. RESULTS: All PPCM patients were discharged within 28 days. In comparison to the control group, PPCM patients had higher rates of preeclampsia (20.4% vs. 1.27%, P<0.001), autoimmune disease (27.3% vs. 11.4%, P = 0.018), and cesarean delivery with preterm labor (31.8% vs. 17.7%, P = 0.037). The neonates of PPCM patients had lower birth weight (2.70±0.66 kg vs. 3.21±0.57 kg, P<0.001). PPCM patients had higher levels of C-reactive protein, d-dimer, brain natriuretic peptide (BNP), and serum phosphorus, but lower levels of albumin and serum calcium (all P<0.001). In all patients with PPCM, the left ventricular ejection fraction (LVEF) returned to normal (≥50%) within 28 days after admission. Subjects with early recovery (n = 34) had lower BNP than those with delayed recovery (n = 10) (649.7 ± 526.0 pg/mL vs. 1444.1 ± 1040.8 pg/mL, P = 0.002). Multivariate regression led to a three-point score system to predict PPCM (1 point each for the presence of pericardial effusion, left ventricular dilatation, and d-dimer level ≥0.5 µg/mL). At a cutoff of ≥2, this scoring system predicted delayed recovery with 95.5% sensitivity and 96.1% specificity. The negative predictive value was 97.4% and the positive predictive value was 93.3%. Binary logistic regression indicated that PPCM patients with pulmonary hypertension, lower hemoglobin, or worse LVEF tended to require longer hospital stay (minimum 14 days). CONCLUSIONS: A risk score that consists of pericardial effusion, left ventricular dilatation, and d-dimer level ≥ 0.5 µg/mL could help streamline the diagnosis of PPCM prior to confirmatory investigations. Moreover, a risk score that consists of pulmonary hypertension, lower hemoglobin and worse LVEF could help to predict poor outcomes in PPCM patients.

Acute Coronary Syndrome May be Associated with Decreased Resolvin D1-to-Leukotriene B4 Ratio.

An imbalance between inflammation-resolving lipid mediators and proinflammatory leukotrienes with the instability of atherosclerotic plaques in experimental models has been reported. However, the contribution of the balance of Resolvin D1 (RvD1) to Leukotriene B4 (LTB4) in predicting acute coronary syndrome (ACS) remains unknown. This study investigated the association of RvD1-to-LTB4 ratio with ACS.Eighty-one patients with ACS and 90 stable coronary artery disease (SCAD) patients were included in this study. Plasma RvD1 and LTB4 levels were measured with commercial kits.Patients with ACS had higher LTB4 levels, lower RvD1 levels, and a lower RvD1-to-LTB4 ratio than patients with SCAD. History of diabetes mellitus, elevated Troponin I, LTB4, and decreased RvD1-to-LTB4 ratio (odds ratio [OR]: 1.025; 95% confidence interval [CI]: 1.014-1.040; P < 0.001) were independently correlated with ACS. Receiver operating characteristic curve analysis demonstrated that RvD1-to-LTB4 ratio was a potential biomarker for the risk of ACS.A circulating proinflammatory lipid profile, characterized by a low RvD1-to-LTB4 ratio may be associated with ACS in patients with ischemic heart disease.

SRC-3 deficiency prevents atherosclerosis development by decreasing endothelial ICAM-1 expression to attenuate macrophage recruitment.

Steroid receptor coactivator 3 (SRC-3) is a member of the p160 SRC family. This factor can interact with multiple nuclear hormone receptors and transcription factors to regulate the expression of their target genes. Although many physiological roles of SRC-3 have been revealed, its role in atherosclerosis is not clear. In this study, we found that SRC-3-/-ApoE-/- mice have reduced atherosclerotic lesions and necrotic areas in their aortas and aortic roots compared with SRC-3+/+ApoE-/- mice after Western diet (WD) feeding for 12 weeks. RNA-Seq and Western blot analyses of the aorta revealed that SRC-3 was required for maintaining the expression of ICAM-1, which was required for macrophage recruitment and atherosclerosis development. siRNA-mediated knockdown of SRC-3 in endothelial cells significantly reduced WD-induced atherosclerotic plaque formation. Additionally, treatment of ApoE-/- mice with SRC-3 inhibitor bufalin prevented atherosclerotic plaque development. SRC-3 deficiency reduced aortic macrophage recruitment. Accordingly, ICAM-1 expression was markedly decreased in the aortas of SRC-3-/-ApoE-/- mice and ApoE-/- mice with endothelial SRC-3 knockdown mediated by AAV9-shSRC-3 virus. Mechanistically, SRC-3 coactivated NF-κB p65 to increase ICAM-1 transcription in endothelial cells. Collectively, these findings demonstrate that inhibiting SRC-3 ameliorates atherosclerosis development, at least in part through suppressing endothelial activation by decreasing endothelial ICAM-1 expression via reducing NF-κB signaling.

An improved procedure for isolating adult mouse cardiomyocytes for epicardial activation mapping.

Cardiovascular disease is a leading cause of death and disability worldwide. Although genetically modified mouse models offer great potential for robust research in vivo, in vitro studies using isolated cardiomyocytes also provide an important approach for investigating the mechanisms underlying cardiovascular disease pathogenesis and drug actions. Currently, isolation of mouse adult cardiomyocytes often relies on aortic retrograde intubation under a stereoscopic microscope, which poses considerable technical barriers and requires extensive training. Although a simplified, Langendorff-free method has been used to isolate viable cardiomyocytes from the adult mouse heart, the system requires enzymatic digestions and continuous manual technical operation. This study established an optimized approach that allows isolation of adult mouse cardiomyocytes and epicardial activation mapping of mouse hearts using a Langendorff device. We used retrograde puncture through the abdominal aorta in vivo and enzymatic digestion on the Langendorff perfusion device to isolate adult mouse cardiomyocytes without using a microscope. The yields of isolated cardiomyocytes were amenable to patch clamp techniques. Furthermore, this approach allowed epicardial activation mapping. We used a novel, simplified method to isolate viable cardiomyocytes from adult mouse hearts and to map epicardial activation. This novel approach could be beneficial in more extensive research in the cardiac field.

Ezetimibe Improves Rosuvastatin Effects on Inflammation and Vascular Endothelial Function in Acute Coronary Syndrome Patients Undergoing PCI.

BACKGROUND: Little is known of the acute effects of ezetimibe in patients with acute coronary syndrome (ACS) undergoing PCI. We investigated whether ezetimibe improves inflammation and vascular endothelial function in patients with ACS undergoing PCI. METHODS: We randomized 171 patients with ACS undergoing PCI to receive ezetimibe 10 mg/day plus rosuvastatin 20 mg/day (combination group, n = 81) versus rosuvastatin 20 mg/day (rosuvastatin group, n = 90). Lipid profile, type II secretory phospholipase A2 (sPLA2-IIa), interleukin-1ß (IL-1ß), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were measured at baseline and after 7 days. Three months after PCI, clinical outcomes were examined. RESULT: The levels of sPLA2-IIa and IL-1ß reduced significantly in both groups, but more when ezetimibe and rosuvastatin were coadministered (sPLA2-IIa: 6.16 ± 2.67 vs. 7.42 ± 3.53 ng/ml, p=0.01; IL-1ß: 37.39 ± 26.25 vs. 48.98 ± 32.26 pg/ml, p=0.01). A significant rise of VCAM-1 and ICAM-1 was observed on day 7 after PCI in the both groups, but was less in the combination group (VCAM-1: 918.28 ± 235.31 vs. 988.54 ± 194.41 ng/ml, p=0.03; ICAM-1: 213.01 ± 100.15 vs. 246.88 ± 105.71 ng/ml, p=0.03). Patients in the combination versus rosuvastatin group appeared to suffer from less major adverse events. Periprocedural therapy of ezetimibe improves rosuvastatin effects on proinflammatory responses and endothelial function associated with ACS patients undergoing PCI. This trial is registered with https://clinicaltrials.gov/ct2/show/ChiCTR-IPR-17012219 (Chinese Clinical Trial Registry, http://www.chictr.org.cn on 02/08/2017).

Association Between Dietary Inflammatory Index and Heart Failure: Results From NHANES (1999-2018).

Objective: To explore the relationship between dietary inflammatory index (DII) and heart failure (HF) in participants with cardiovascular and cerebrovascular diseases. Methods: NHANES (1998-2018) data were collected and used to assess the association of HF with DII. Twenty-four-hour dietary consumptions were used to calculate the scores of DII. Demographic characteristics and physical and laboratory examinations were collected for the comparison between HF and non-HF groups. Logistic regression analysis and random forest analysis were performed to calculate the odds rate and determine the potential beneficial dietary components in HF. Results: A total of 19,067 cardiac-cerebral vascular disease participants were categorized as HF (n = 1,382; 7.25%) and non-HF (n = 17,685; 92.75%) groups. Heart failure participants had higher levels of DII score compared with those in the non-HF group (0.239 ± 1.702 vs. -0.145 ± 1.704, p < 0.001). Compared with individuals with T1 (DII: -3.884 to -0.570) of DII, those in T3 (DII: 1.019 to 4.598) had a higher level of total cholesterol (4.49 ± 1.16 vs. 4.75 ± 1.28 mmol/L, p < 0.01), globulin (29.92 ± 5.37 vs. 31.29 ± 5.84 g/L, p < 0.001), and pulse rate (69.90 ± 12.22 vs. 72.22 ± 12.77, p < 0.001) and lower levels of albumin (40.76 ± 3.52 vs. 39.86 ± 3.83 g/L, p < 0.001), hemoglobin (13.76 ± 1.65 vs. 13.46 ± 1.77 g/dl, p < 0.05), and hematocrit (40.83 ± 4.69 vs. 40.17 ± 5.01%, p < 0.05). The odds rates of HF for DII from the logistic regression were 1.140, 1.158, and 1.110 in models 1, 2, and 3, respectively. In addition, from the results of random forest analysis, dietary magnesium, fiber, and beta carotene may be essential in HF. Conclusion: Dietary inflammatory index was positively associated with HF in US adults, and dietary intervention might be a promising method in the therapy of HF.

Inhibited HDAC3 or Elevated MicroRNA-494-3p Plays a Protective Role in Myocardial Ischemia-Reperfusion Injury via Suppression of BRD4.

Increased histone deacetylase 3 (HDAC3) has been demonstrated to contribute to the pathogenesis of myocardial ischemia-reperfusion injury (MI/RI). Therefore, the goal of this study was to investigate how HDAC3 regulated MI/RI by mediating microRNA (miR)-494-3p/dromodomain-containing protein 4 (BRD4) axis. The MI/RI model was established by ligating the right anterior descending coronary artery. Cardiomyocytes from newborn mice were treated with hypoxia/reoxygenation (H/R). Gain-of-function and loss-of-function approaches were implemented to figure out the roles of miR-494-3p and HDAC3 in MI/RI. miR-494-3p, HDAC3, and BRD4 in myocardial tissues of mice with MI/RI and H/R-treated cardiomyocytes were detected. The relationships between miR-494-3p and HDAC3 and BRD4 were identified. Reduced miR-494-3p and upregulated HDAC3 and BRD4 exhibited in myocardial tissues of mice with MI/RI and H/R-treated cardiomyocytes. Inhibited HDAC3 or elevated miR-494-3p repressed the inflammation and apoptosis, improved cardiac function, and ameliorated myocardial injury in myocardial tissues of mice with MI/RI. Suppression of HDAC3 or elevation of miR-494-3p depressed inflammation and apoptosis and promoted cell viability of primary cardiomyocytes. miR-494-3p targeted BRD4. The study concludes that suppressed HDAC3 plays a protective role in MI/RI by upregulation of miR-494-3p and inhibition of BRD4, which could be helpful for MI/RI therapy.

Comparison of coronary artery bypass grafting and percutaneous coronary intervention for syphilitic coronary artery ostial lesions: A 4-year retrospective study.

This study investigated the efficacy of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in treatment of patients with syphilitic coronary artery ostial lesions (SCAOL).Sixty SCAOL patients were divided into two groups according to the different treatments: the CABG group (n = 32) and the PCI group (n = 28). We determined serum levels of ß-type natriuretic peptide (BNP) and cardiac function, and evaluated treatment efficacy such as the rates of restenosis, patency, and major adverse cardiovascular events (MACEs) during hospital stay and the effects of antisyphilis and different types of CABG on restenosis during the 6-month follow-up period.There were no statistical differences in demographic or baseline clinical characteristics, BNP levels, left ventricular end-diastolic diameter (LVDd), or ejection fraction (EF) between the CABG and PCI groups at 1 week after surgery, However, after 6-month of follow-up, the CABG group had a significantly lower rate of coronary artery restenosis, lower incidence of MACEs, and better cardiac function than the PCI group. Within the CABG group, the left internal mammary artery (LIMA) subgroup had a lower restenosis rate than the saphenous vein graft (SVG) subgroup. In addition, patients who had received anti-syphilis therapy had a significantly lower restenosis rate than those without anti-syphilis therapy at 6-month post-surgery.Compared with patients who received PCI, patients who received CABG had better prognoses. LIMA has a better therapeutic efficacy than SVG in terms of the restenosis rate, and anti-syphilis treatment significantly reduces the restenosis rate, compared with non-anti-syphilis treatment.