Serum apolipoprotein A-I depletion is causative to silica nanoparticles-induced cardiovascular damage.

The rapid development of nanotechnology has greatly benefited modern science and engineering and also led to an increased environmental exposure to nanoparticles (NPs). While recent research has established a correlation between the exposure of NPs and cardiovascular diseases, the intrinsic mechanisms of such a connection remain unclear. Inhaled NPs can penetrate the air-blood barrier from the lung to systemic circulation, thereby intruding the cardiovascular system and generating cardiotoxic effects. In this study, on-site cardiovascular damage was observed in mice upon respiratory exposure of silica nanoparticles (SiNPs), and the corresponding mechanism was investigated by focusing on the interaction of SiNPs and their encountered biomacromolecules en route. SiNPs were found to collect a significant amount of apolipoprotein A-I (Apo A-I) from the blood, in particular when the SiNPs were preadsorbed with pulmonary surfactants. While the adsorbed Apo A-I ameliorated the cytotoxic and proinflammatory effects of SiNPs, the protein was eliminated from the blood upon clearance of the NPs. However, supplementation of Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. In addition, we found a further declined plasma Apo A-I level in clinical silicosis patients than coronary heart disease patients, suggesting clearance of SiNPs sequestered Apo A-I to compromise the coronal protein's regular biological functions. Together, this study has provided evidence that the protein corona of SiNPs acquired in the blood depletes Apo A-I, a biomarker for prediction of cardiovascular diseases, which gives rise to unexpected toxic effects of the nanoparticles.

Association between the insulin resistance marker TyG index and subsequent adverse long-term cardiovascular events in young and middle-aged US adults based on obesity status.

BACKGROUND: A lthough the triglyceride-glucose (TyG) index has been shown to closely correlate with cardiometabolic outcomes and predict cardiovascular events in many groups, it remains unclear whether obese status in young and middle-aged adults is associated with long-term unfavorable cardiovascular events. This warrants further investigation. METHODS: This retrospective cohort study analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999-2018, with follow-up for mortality status until December 31, 2019. To categorize participants based on the TyG level, the optimal critical value was determined through restricted cubic spline function analysis, dividing them into high and low TyG groups. The study assessed the relationship between TyG and cardiovascular events and all-cause mortality in young and middle-aged adults stratified by obesity status. Kaplan‒Meier and Cox proportional risk models were used to analyze the data. RESULTS: During a follow-up period of 123 months, a high TyG index increased the risk of cardiovascular events by 63% (P = 0.040) and the risk of all-cause mortality by 32% (P = 0.010) in individuals after adjusting for all covariates. High TyG was shown to be linked to cardiovascular events in obese people (Model 3: HR = 2.42, 95% CI = 1.13-5.12, P = 0.020); however, there was no significant difference in TyG groups for nonobese adults in Model 3 (P = 0.08). CONCLUSIONS: TyG was independently associated with harmful long-term cardiovascular events in young and middle-aged US populations, with a stronger association observed in those who were obese.

GALNT4 primes monocytes adhesion and transmigration by regulating O-Glycosylation of PSGL-1 in atherosclerosis.

Atherosclerosis is a major underlying cause of cardiovascular disease. Genome wide association studies have predicted that GalNAc-T4 (GALNT4), which responsible for initiating step of mucin-type O-glycosylation, plays a causal role in the susceptibility to cardiovascular diseases, whereas the precise mechanism remains obscure. Thus, we sought to determine the role and mechanism of GALNT4 in atherosclerosis. Firstly, we found the expression of GALNT4 and protein O-glycosylation were both increased in plaque as atherosclerosis progressed in ApoE-/- mice by immunohistochemistry. And the expression of GALNT4 was also increased in human monocytes treated with ACS (acute coronary syndrome) sera and subjected to LPS and ox-LDL in vitro. Moreover, silencing expression of GALNT4 by shRNA lentivirus alleviated atherosclerotic plaque formation and monocyte/macrophage infiltration in ApoE-/- mice. Functional investigations demonstrate that GALNT4 knockdown inhibited P-selectin-induced activation of ß2 integrin on the surface of monocytes, decreased monocytes adhesion under flow condition with P-selectin stimulation, as well as suppressed monocytes transmigration triggered by monocyte chemotactic protein- 1(MCP-1). In contrast, GALNT4 overexpression enhanced monocytes adhesion and transmigration. Furthermore, Vicia Villosa Lectin (VVL) pull down and PSGL-1 immunoprecipitation assays showed that GALNT4 overexpression increased O-Glycosylation of PSGL-1 and P-selectin induce phosphorylation of Akt/mTOR and IκBα/NFκB on monocytes. Conversely, knockdown of GALNT4 decreased VVL binding and attenuated the activation of Akt/mTOR and IκBα/NFκB. Additionally, mTOR inhibitor rapamycin blocked these effects of GALNT4 overexpression on monocytes. Collectively, GALNT4 catalyzed PSGL-1 O-glycosylation that involved in P-selectin induced monocytes adhesion and transmigration via Akt/mTOR and NFκB pathway. Thus, GALNT4 may be a potential therapeutic target for atherosclerosis.

Nutrition-related diseases and cardiovascular mortality in American society: national health and nutrition examination study, 1999-2006.

BACKGROUND: Despite many significant advances in treatment and management, cardiovascular disease remains the main cause of the global disease burden. Nutrition-related disease is a modifiable cardiovascular risk factor. However, few studies have examined the relationship between nutrition-related diseases and cardiovascular mortality. OBJECTIVE: We aimed to investigate the association of nutrition-related diseases with cardiovascular mortality based on a large nationally representative community population. DESIGN: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 with mortality follow-up through December 31, 2015. Finally, 12,469 participants were analyzed. Each participant was assigned to one of four groups: normal nutrition without sarcopenia, sarcopenia with normal nutrition, malnutrition without sarcopenia, and malnutrition-sarcopenia syndrome. Survival curves and Cox regressions based on the NHANES recommended weights were used to assess the association between nutrition-related diseases and cardiovascular mortality. RESULTS: Of the 12,469 patients included in the study and divided into four groups, malnutrition-sarcopenia syndrome had the highest 5- and 10-year cardiovascular mortality rates. After adjustment for related factors, sarcopenia with normal nutrition (hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.28-2.06; P < 0.001), malnutrition without sarcopenia (HR: 1.28, 95% CI:1.03-1.58; P = 0.024), and malnutrition-sarcopenia syndrome (HR: 2.66, 95% CI:1.89 - 3.74; P < 0.001) were significantly associated with increased risk of all-cause mortality. Malnutrition-sarcopenia syndrome remained associated with an increased risk of cardiovascular mortality (HR: 3.56, 95% CI: 1.17 - 10.84; P < 0.001). CONCLUSIONS: Malnutrition-sarcopenia syndrome was highly prevalent among community-dwelling adults in the United States and was a strong prognostic factor for cardiovascular mortality in the community setting. Randomized clinical trials are needed to demonstrate whether prevention or treatment of malnutrition-sarcopenia syndrome in community populations can reduce global cardiovascular mortality.

Assessment of late gadolinium enhancement-negative chronic total occlusion by longitudinal strain analysis using cardiac magnetic resonance imaging.

BACKGROUND: Strain analysis has become commonly used in clinical practice in various heart diseases. PURPOSE: To explore whether late gadolinium enhancement (LGE)-negative areas with coronary artery chronic total occlusion (CTO) appear normal when analyzed for longitudinal strain using cardiac magnetic resonance (CMR) imaging. MATERIAL AND METHODS: A total of 16 patients and 31 healthy controls who underwent 1.5-T MR at our hospital between January 2015 and July 2017 were included in the study. The LGE-CMR of patients with CTO was negative. Left ventricular functional parameters, segmental longitudinal strain/strain rate, and perfusion parameters were measured using CVI42 software. RESULTS: For myocardial segments supplied by CTO vessels, systolic longitudinal strain rate (SLSR)was significantly lower than that of healthy controls, and diastolic longitudinal strain rate (DLSR) was significantly higher (1.19 1/s vs. 1.02 1/s; P = 0.018). Moreover, longitudinal strain (LS), SLSR, and DLSR did not differ between good and poor collateral circulation. Perfusion index of CTO territory segments was lower than non-CTO territory segments (0.20 vs. 0.22; P = 0.027). No correlation was found between longitudinal strain parameters and perfusion parameters. CONCLUSION: Although LGE-CMR was negative in patients with CTO, the myocardial SLSR of CTO territory segments was significantly lower than that of healthy controls.

Subtraction improves the accuracy of coronary CT angiography for detecting obstructive disease in severely calcified segments.

OBJECTIVE: To investigate the accuracy, diagnostic confidence, and interobserver agreement of subtraction coronary CT angiography (CCTA) versus invasive coronary angiography on 320-row CT in coronary segments with severe or non-severe calcification. MATERIALS/METHODS: Sixty-four patients (33 men, 66.6 ± 8.2 years) with suspected coronary artery disease (CAD) were prospectively enrolled from October 2019 to June 2020. The cross-sectional circumferential extent of calcification was used to classify calcified segments as non-severely ( < 180°) or severely calcified ( ≥ 180°). Three independent, blinded radiologists evaluated the severity of coronary stenosis. Interobserver agreement was evaluated using Fleiss' kappa (κ). A multiple-reader multiple-case receiver operating characteristic (ROC) method was conducted, and diagnostic accuracy was measured using the mean areas under the ROC curves (AUCs), with ≥ 50% stenosis as a cut-off. Diagnostic confidence, diagnostic accuracy, and interobserver agreement were compared between CCTA with or without subtraction information in severely and non-severely calcified segments. RESULTS: In cases with severe calcification (51 patients, 146 segments), CCTA with subtraction information achieved better diagnostic accuracy (per-patient AUC: 0.73 vs 0.57, p = 0.03; per-segment AUC: 0.85 vs 0.62, p = 0.01), diagnostic confidence (3.7 vs 2.6, p < 0.001), and interobserver agreement (κ: 0.59 vs 0.30). Diagnostic accuracy (per-patient AUC: 0.81 vs 0.93, p = 0.30; per-patient AUC: 0.79 vs 0.82, p = 0.54) was not increased in cases with non-severe calcification (13 patients, 190 segments). CONCLUSIONS: CCTA with subtraction information achieved better diagnostic accuracy in cases of severe calcification (circumferential extent ≥ 180°). However, for non-severe calcification (circumferential extent < 180°), the effect of calcium subtraction was unclear, as it did not improve diagnostic accuracy. KEY POINTS: • Subtraction coronary CT angiography achieves better diagnostic accuracy, higher diagnostic confidence, and increased interobserver agreement for severe calcification (circumferential extent ≥ 180°). • Calcium subtraction does not improve the diagnostic accuracy of coronary CT angiography for calcification with a circumferential extent of < 180°.

Two-year left ventricular systolic function of percutaneous coronary intervention vs optimal medical therapy for patients with single coronary chronic total occlusion.

In this study, two-dimensional speckle tracking echocardiography (2D-STE) and real-time three-dimensional echocardiography (RT-3DE) were applied to compare the changes of left ventricular systolic function associated with percutaneous coronary intervention (PCI) versus optimal medical therapy (OMT) in patients with single chronic total occlusion (CTO). 63 single CTO patients (age 61.88 ± 8.86 years) were examined by echocardiography and were divided into the PCI group (n = 27) and OMT group (n = 36) according to the initial treatment strategy. Two-dimensional left ventricular ejection fraction (2D-LVEF), two-dimensional indexed left ventricular end-systolic volume (2D-LVESVI), and two-dimensional indexed left ventricular end-diastolic volume (2D-LVEDVI) were measured using two-dimensional echocardiography (2DE). Three-dimensional left ventricular ejection fraction (3D-LVEF), three-dimensional indexed left ventricular end-systolic volume (3D-LVESVI), and three-dimensional indexed left ventricular end-diastolic volume (3D-LVEDVI) were measured using RT-3DE. Global circumferential strain (GCS) and global longitudinal strain (GLS) were measured using 2D-STE. After 2 years of follow-up, there were no significant differences in the 2D-LVEF, 2D-LVESVI, 3D-LVEF, 3D-LVESVI, 3D-LVEDVI, and GCS, except for GLS (P = .001) between the CTO-PCI and CTO-OMT groups. GLS decreased significantly in OMT group (P = .016) in contrast with PCI group in which GLS increased significantly (P = .007). Left ventricular systolic function assessment using 2D-STE showed a significant difference in GLS between CTO-PCI and CTO-OMT. And the patients who chose PCI revascularization at the 2-year follow-up had better left ventricular systolic function improvement than those who were conservatively treated with OMT.

Long-term outcomes of medical therapy versus successful recanalisation for coronary chronic total occlusions in patients with and without type 2 diabetes mellitus.

BACKGROUND: In this study, we compared the outcomes of medical therapy (MT) with successful percutaneous coronary intervention (PCI) in chronic total occlusions (CTO) patients with and without type 2 diabetes mellitus. METHODS: A total of 2015 patients with CTOs were stratified. Diabetic patients (n = 755, 37.5%) and non-diabetic patients (n = 1260, 62.5%) were subjected to medical therapy or successful CTO-PCI. We performed a propensity score matching (PSM) to balance the baseline characteristics. A comparison of the major adverse cardiac events (MACE) was done to evaluate long-term outcomes. RESULTS: The median follow-up duration was 2.6 years. Through multivariate analysis, the incidence of MACE was significantly higher among diabetic patients compared to the non-diabetic patients (adjusted hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.09-1.61, p = 0.005). Among the diabetic group, the rate of MACE (adjusted HR 0.61, 95% CI 0.42-0.87, p = 0.006) was significantly lower in the successful CTO-PCI group than in the MT group. Besides, in the non-diabetic group, the prevalence of MACE (adjusted HR 0.85, 95% CI 0.64-1.15, p = 0.294) and cardiac death (adjusted HR 0.94, 95% CI 0.51-1.70, p = 0.825) were comparable between the two groups. Similar results as with the early detection were obtained in propensity-matched diabetic and non-diabetic patients. Notably, there was a significant interaction between diabetic or non-diabetic with the therapeutic strategy on MACE (p for interaction = 0.036). CONCLUSIONS: For treatment of CTO, successful CTO-PCI highly reduces the risk of MACE in diabetic patients when compared with medical therapy. However, this does not apply to non-diabetic patients.

Clinical Outcomes of Bivalirudin Versus Heparin in Elderly Patients Undergoing Percutaneous Coronary Intervention: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

PURPOSE: The aim of this study was to explore the safety and efficacy of bivalirudin in elderly patients undergoing percutaneous coronary intervention (PCI). METHODS: An electronic search was conducted for randomized controlled trials with outcomes of interest in the elderly (≥ 65 years of age). Pooled risk ratios (RR) and 95% confidence interval (CI) using random effects Der Simonian-Laird models were calculated. Primary outcomes were net adverse clinical events (NACE) and major bleeding events at 30 days. Secondary outcomes were major adverse cardiac events (MACE) at 30 days. MACE, all-cause mortality, and NACE at 6-12 months were also examined. RESULTS: Eleven trials that randomized a total of 15,895 elderly patients undergoing PCI to bivalirudin versus heparin were included. At 30 days, bivalirudin was associated with a reduced risk of NACE (0.86 [0.75-0.99], p = 0.04), mainly driven by reduction in major bleeding events (0.66 [0.54-0.80], p < 0.0001), as compared with heparin. On subgroup analyses based on the use of GPI in the heparin arm, benefit of major bleeding associated with bivalirudin appeared to be equally evident when GPI was used as a bailout (0.66 [0.46-0.94], p = 0.02) versus routine (0.67 [0.51-0.88], p = 0.004) adjunctive therapy with heparin. Subgroup analyses stratified by clinical presentation showed that benefit of bivalirudin in reducing NACE was even more obvious in the elderly group presenting with ST segment elevation myocardial infarction (STEMI) (0.76 [0.65-0.89], p = 0.0007), as compared with the overall (acute coronary syndrome or stable ischemic heart disease) group. No difference in MACE (0.94 [0.82-1.09], p = 0.42) was demonstrated between the two groups. Bivalirudin was associated with a similar risk of NACE (0.74 [0.39-1.42], p = 0.36) at 6 months and MACE (0.90 [0.68-1.19], p = 0.45) at 6-12 months, while a non-statistically significant trend toward lower all-cause mortality (0.70 [0.47-1.06], p = 0.09) at 1 year. CONCLUSION: In elderly patients undergoing PCI, bivalirudin was associated with a lower risk of major bleeding events and the magnitude of benefit was not related to the use of GPI and irrespective of clinical presentation. Bivalirudin may reduce the NACE, particularly in elderly patients presenting with STEMI or in the setting of routine GPI use in the heparin arm, while no difference in MACE was demonstrated between the two groups.

Gender Differences in Long-Term Outcomes of Medical Therapy and Successful Percutaneous Coronary Intervention for Coronary Chronic Total Occlusions.

BACKGROUND: There is a paucity of information about the gender differences in clinical outcomes of successful percutaneous coronary intervention (PCI) compared with medical therapy (MT) in patients with coronary chronic total occlusions (CTOs). OBJECTIVES: We aimed to investigate the impact of gender on long-term clinical outcomes associated with successful CTO-PCI versus MT in patients with CTOs. METHODS: Between January 2007 and December 2016, a total of 1702 patients with ≥1 CTO were enrolled. After exclusion, 1294 patients with 1520 CTOs were analyzed and were divided into the female group (n = 304, 23.5%) and the male group (n = 990, 76.5%). The patients in the female or male group were assigned to a MT group or successful CTO-PCI group according to the treatment strategy. In the female group, they were divided into two groups: 177 patients in the MT group and 127 patients in the successful CTO-PCI group. In the male group, they were divided into two groups: 623 patients in the MT group and 367 patients in the successful CTO-PCI group. The primary outcome was cardiac death. The secondary outcome was major adverse cardiac event (MACE). RESULTS: The median overall follow-up duration was 3.6 (IQR, 2.1-5.0) years, there were no significant differences between the MT and successful CTO-PCI groups with respect to the prevalence of cardiac death (MT vs. successful PCI: 6.8% vs. 3.9%, p=0.287) and MACE (20.9% vs. 21.3%, p=0.810) in female patients. In the male group, the occurrence of cardiac death (MT vs. successful PCI: 6.6% vs. 3.8%, p=0.066) was similar between the two groups. The MACE rate (30.0% vs. 18.5%, p < 0.001) was significantly higher in the MT group. Heart failure (hazard ratio 3.40, 95% confidence interval 1.23-9.40, p=0.018) was an independent predictor of cardiac death in female patients. CONCLUSIONS: Successful CTO-PCI was not associated with reduced risk of cardiac death compared with medical therapy alone in both female and male patients. However, men have a significant reduction in MACE rate after successful CTO-PCI. Aggressive CTO-PCI should be considered carefully among female patients.

Successful recanalisation of coronary chronic total occlusions is not associated with improved cardiovascular survival compared with initial medical therapy.

Objective. To compare the clinical outcomes associated with successful percutaneous coronary intervention (PCI) versus initial medical therapy (MT) in patients with coronary chronic total occlusions (CTOs). Methods. Between January 2007 and December 2016, a total of 1702 patients with ≥1 CTO were enrolled. Patients who had a failed CTO-PCI were excluded. After exclusion, 1294 patients with 1520 CTOs were divided into the MT group initially (did not undergo a CTO-PCI attempt) (n = 800) and successful PCI group (n = 494). Propensity-score matching was also performed to adjust for baseline characteristics. The primary outcome was cardiac death. Results. The median overall follow-up duration was 3.6 (IQR, 2.1-5.0) years, there was no significant difference between the two groups with respect to the prevalence of cardiac death (MT vs. successful PCI: 6.6 vs. 3.8%, adjusted hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.41-2.14, p = .867). In the propensity-matched population (286 pairs), there were no significant differences in the prevalence of cardiac death (MT vs. successful PCI: 5.9% vs. 3.1%, HR 0.51, 95% CI 0.23-1.15, p = .104) and major adverse cardiovascular events (MACE) (HR 0.76, 95% CI 0.53-1.09, p = .130) between the two groups. Conclusion. In the treatment of patients with CTOs, successful PCI is not associated with improved long-term cardiovascular survival or reduced the risk of MACE compared with MT alone initially.

A Peptide Analogue of Selectin Ligands Attenuated Atherosclerosis by Inhibiting Monocyte Activation.

BACKGROUND: Circulating monocytes play a critical role in the pathogenesis of atherosclerosis. Monocyte homing to sites of atherosclerosis is primarily initiated by selectin. Thus, blockade of the interaction of selectins and their ligands holds a significant role in monocyte homing which might be a potential approach to treat atherosclerosis. Here, we investigated the efficacy of a novel peptide analogue of selectin ligands IELLQAR in atherosclerosis. METHODS AND RESULTS: In this study, we firstly measured the effect of the IELLQAR selectin-binding peptide on the inhibition of binding of selectins to monocytes by flow cytometry, which exhibited a dose-dependent inhibitory effect on the binding of the P-, E-, and L-selectins to monocytes, especially the inhibition of P-selectin binding to human peripheral blood monocytes (PBMCs) (half maximal inhibitory concentration (IC50~5 µM)) and THP-1 cells (IC50~10 µM). Furthermore, IELLQAR inhibited P-selectin-induced activation of CD11b on the surface of monocytes and decreased adhesion of monocytes to the endothelium. ApoE-/- mice with or without IELLQAR (1 or 3 mg/kg) fed a Western-type diet (WTD) or which had disturbed blood flow-induced shear stress underwent partial left carotid artery ligation (PLCA) to induce atherosclerosis. In the WTD- and PLCA-induced atherosclerosis models, atherosclerotic plaque formation and monocyte/macrophage infiltration of the arterial wall both decreased in ApoE-/- mice treated with the IELLQAR peptide. Our results also revealed that IELLQAR inhibited the differentiation of monocytes into macrophages through P-selectin-dependent activation of the nuclear factor- (NF-) κB and mammalian target of rapamycin (mTOR) pathways. CONCLUSION: Collectively, our results demonstrated that IELLQAR, a peptide analogue of selectin ligands, inhibited selectin binding to monocytes, which led to subsequent attenuation of atherosclerosis via inhibition of monocyte activation. Hence, use of the IELLQAR peptide provides a new approach and represents a promising candidate for the treatment of atherosclerosis in the early stage of disease.

Gender and Age Differences Associated With Prehospital Delay in Chinese Patients Presenting With ST-Elevation Myocardial Infarction.

BACKGROUND AND OBJECTIVES: A limited number of studies have examined the interaction between gender and age with regard to extent of prehospital delay. Our aim was to examine gender and age differences associated with prehospital delay in Chinese patients presenting with ST-elevation myocardial infarction (STEMI). METHODS: A total of consecutive 1429 records from patients presenting with STEMI were analyzed between June 1, 2009, and June 1, 2010. We compared hospital care data by gender and age for inpatients with acute STEMI presenting within 24 hours of symptom onset. RESULTS: The overall median duration of prehospital delay was 150 minutes (mean, 266 minutes). For patients 54 years or younger, 55 to 64 years old, and 75 years or older, women were more likely to experience longer delays compared with men (P < .05) even after controlling for medical history and risk factors. For male patients, compared with groups 54 years or younger, with the exception of men 55 to 64 years old, older male patients were more likely to have greater delays (P < .05) even after controlling for medical history and risk factors. However, after controlling for other variables, these gender and age differences in prehospital delay were no longer statistically significant. Among patients 65 to 74 years old, there were no gender differences in prehospital delay. Among female patients, there were no age differences in prehospital delay. CONCLUSIONS: Male elderly patients (aged ≥65 years) and women (aged ≤64 and ≥75 years) with STEMI were more likely to delay seeking timely medical care. These gender and age differences were explained by different education, stable income, medical insurance, typical chest pain, and cognition toward heart diseases.

[Low-density lipoprotein cholesterol target goal attainment rate and related factors in patients with acute coronary syndrome after percutaneous coronary intervention].

OBJECTIVE: To observe the low-density lipoprotein cholesterol (LDL-C) target goal attainment rate and related factors in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). METHODS: From March 2011 to March 2012, a total of 832 ACS patients were retrospectively evaluated in the Cardiology Department of the First Affiliated Hospital of Dalian Medical University. The target goal attainment rate after PCI was defined as the percentage of patients reaching LDL-C goals recommended by The European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias (European guidelines) and Chinese guidelines on prevention and treatment of dyslipidemias in adults and Chinese guidelines on percutaneous coronary artery intervention treatment (Chinese guidelines). Multivariate logistic regression analysis was used to analyze the related factors. RESULTS: According to the European guidelines, the overall LDL-C goal attainment rates at 1 month and 9 months after PCI were 25.2% (210/832) and 22.2% (186/832), respectively. According to the Chinese guidelines, the overall LDL-C goal attainment rates at 1 month and 9 months after PCI were 46.5% (387/832) and 42.3% (352/832), respectively. In accordance with the Chinese guidelines, the multivariate logistic regression analysis showed that gender (females/males, OR = 0.650, 95%CI: 0.442-0.956), age ( ≥ 60 years/<60 years, OR = 0.628, 95%CI:0.464-0.850), hypertension (OR = 0.737, 95%CI: 0.547-0.994), prior myocardial infarction history (OR = 0.696, 95%CI:0.511-0.948), prior PCI history (OR = 0.575, 95%CI: 0.339-0.974) and baseline LDL-C levels ( OR = 0.155, 95%CI: 0.096-0.252) were independent risk factors that affected LDL-C goal attainment at 1 month post PCI. Moreover, the following parameters were the independent risk factors for LDL-C goal attainment at 9 months after PCI: prior myocardial infarction history (OR = 0.706, 95%CI:0.521-0.958), prior PCI history (OR = 0.565, 95%CI:0.334-0.957) and baseline LDL-C levels (OR = 0.176, 95%CI:0.110-0.282). CONCLUSIONS: Currently, the LDL-C control rate is low in patients with ACS after PCI. The cholesterol lowering therapy should be individually strengthened for patients after PCI, especially in female patients, patients with aged ≥ 60 years old, hypertension, prior myocardial infarction history, prior PCI history and higher baseline LDL-C level.

M2 macrophage-derived exosomes promote angiogenesis and improve cardiac function after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. The intercellular communication in post-infarction angiogenesis remains unclear. METHODS: In this study, we explored the role and mechanism of action of M2 macrophage-derived exosomes (M2-exos) in angiogenesis after MI. M2-exos were harvested and injected intramyocardially at the onset of MI. Two distinct endothelial cells (ECs) were cultured with M2-exos to explore the direct effects on angiogenesis. RESULTS: We showed that M2-exos improved cardiac function, reduced infarct size, and enhanced angiogenesis after MI. Moreover, M2-exos promoted angiogenesis in vitro; the molecules loaded in the vesicles were responsible for its proangiogenic effects. We further validated that higher abundance of miR-132-3p in M2-exos, which recapitulate their functions, was required for the cardioprotective effects exerted by M2-exos. Mechanistically, miR-132-3p carried by M2-exos down-regulate the expression of THBS1 through direct binding to its 3´UTR and the proangiogenic effects of miR-132-3p were largely reversed by THBS1 overexpression. CONCLUSION: Our findings demonstrate that M2-exos promote angiogenesis after MI by transporting miR-132-3p to ECs, and by binding to THBS1 mRNA directly and negatively regulating its expression. These findings highlight the role of M2-exos in cardiac repair and provide novel mechanistic understanding of intercellular communication in post-infarction angiogenesis.

Erratum: [Corrigendum] Downregulated caveolin­1 expression serves a potential role in coronary artery spasm by inducing nitric oxide production in vitro.

[This corrects the article DOI: 10.3892/etm.2018.6646.].

Association between novel inflammatory markers and non-alcoholic fatty liver disease: a cross-sectional study.

OBJECTIVE: This study aimed to investigate the association between novel inflammatory markers (NIMs) and non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 6306 subjects were enrolled in this cross-sectional study. NIMs, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), C-reactive protein to albumin ratio (CAR), lymphocyte to monocyte ratio (LMR), systemic immune-inflammation index (SII) and prognostic nutritional index (PNI), were calculated. The prevalence of NAFLD and its association with NIMs were assessed by multivariable logistic regression analysis. Subgroup analysis were performed based on age, sex and BMI. RESULTS: The prevalence of NAFLD was 52.5% in the study population. Compared with non-NAFLD subjects, NAFLD patients were older and more frequent in females. The prevalence of NAFLD progressively increased among the higher quartile groups of CAR, LMR, SII and PNI ( P -trend < 0.05), whereas it progressively decreased among the higher quartile group of NLR and PLR ( P -trend < 0.05). According to multivariable logistic regression analysis, the highest quartile (Q4) had a significantly higher risk of NAFLD compared with Q1 in LMR [odds ratio (OR): 1.43; 95% confidence interval (CI): 1.17-1.75; P -trend < 0.001] and PNI (OR: 1.92; 95% CI: 1.57-2.35; P -trend < 0.001). The subgroup analysis showed a stronger association of PNI with NAFLD. CONCLUSION: The study highlights the association between NIMs and NAFLD, with LMR and PNI identified as potential non-invasive markers of inflammation in NAFLD. Specifically, PNI exhibited the strongest association and may serve as a valuable marker for assessing inflammation in NAFLD.

Effects of selenoprotein S on oxidative injury in human endothelial cells.

BACKGROUND: Selenoprotein S (SelS) is an important endoplasmic reticulum and plasma membrane-located selenoprotein implicated in inflammatory responses and insulin resistance. However, the effects of SelS on endothelial cells (ECs) have not been reported. In the present study, the role of SelS in oxidative stress and the underlying mechanism were investigated in human ECs. METHODS: A SelS over-expression plasmid (pc-SelS) and a SelS-siRNA plasmid were transfected into human umbilical vein endothelial cells (American Type Culture Collection, USA). The cells were divided into four groups: control, SelS over-expression (transfected with pc-SelS), vector control, and SelS knockdown (transfected with siRNA-SelS). After treating the cells with H2O2, the effects of oxidative stress and the expression of caveolin-1 (Cav-1) and protein kinase Cα (PKCα) were investigated. RESULTS: Following treatment with H2O2, over-expression of SelS significantly increased cell viability and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) production and Cav-1 gene and protein expression. However, no effects on PKCα were observed. In contrast, knockdown of SelS significantly decreased cell viability, SOD activity, and PKCα gene and protein expression, and increased MDA production and Cav-1 gene and protein expression. CONCLUSIONS: SelS protects ECs from oxidative stress by inhibiting the expression of Cav-1 and PKCα.