Yingxin Zhao

Background and Aims: Epicardial adipose tissue, exosomes, and miRNAs have important activities in atherosclerosis. The purpose of this study was to establish miRNA expression profiles of epicardial adipose tissue-derived exosomes in patients with coronary atherosclerosis. Methods: Biopsies of epicardial adipose tissue were obtained from patients with and without coronary artery disease (CAD, n = 12 and NCAD, n = 12) during elective open-heart surgeries. Tissue was incubated with DMEM-F12 for 24 hours. Exosomes were isolated, then nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting were performed to confirm the existence of exosomes. Total RNA in exosomes was subjected to high-throughput sequencing to identify differentially expressed miRNAs. MicroRNA target gene prediction was performed, and target genes were analyzed by Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and mirPath to identify function. Reverse transcription quantitative PCR was performed to confirm the differentially expressed miRNAs. Results: Fifty-three unique miRNAs were identified (adjusted p < 0.05, fold of change >2), among which 32 miRNAs were upregulated and 21 miRNAs were downregulated in coronary artery disease patients. Reverse transcription quantitative PCR validated the results for seven miRNAs including miR-141-3p, miR-183-5p, miR-200a-5p, miR-205-5p, miR-429, miR-382-5p and miR-485-3p, with the last two downregulated. GO and KEGG analysis by mirPath indicated that these differentially expressed miRNAs were enriched in cell survival, apoptosis, proliferation, and differentiation. Conclusions: Coronary artery disease patients showed differential epicardial adipose tissue exosomal miRNA expression compared with patients without coronary artery disease. The results provide clues for further studies of mechanisms of atherosclerosis.

Aims: This study intends to explore whether, or to what extent, the estimated remnant-like particle cholesterol was associated with coronary collateralization in patients with chronic total occlusion lesions. Methods: 792 patients with at least one coronary chronic total occlusion lesion were enrolled. Serum level of lipid profiles were determined and the estimated remnant-like particle cholesterol was calculated. The development of coronary collateralization was graded as low (Rentrop score 0–1) or high (Rentrop score 2–3) collateralization according to the Rentrop classification system and then the association between the estimated remnant-like particle cholesterol and collateralization was assessed. Results: 222 participants were classified into low collateralization group. The estimated remnant-like particle cholesterol level was significantly higher in low collateralization (P < 0.001) and type 2 diabetes mellitus (P = 0.009) group. To further explore the association between the estimated remnant-like particle cholesterol and the development of coronary collateralization, these patients were divided into 3 groups based on the estimated remnant-like particle cholesterol tertiles. The prevalence of low collateralization increased stepwise with the tertile groups (T1 12.5% vs. 27.1% vs. 45.3%, P < 0.001). Multivariate logistic regression analysis showed that the estimated remnant-like particle cholesterol was independently associated with the under-developed collateralization, with an OR and 95%CI of 2.34 (1.46–3.74) and 4.91 (3.01–8.02) in the T2 and T3 group, respectively. The following receiver-operating characteristic analysis indicated that the diagnostic value of estimated remnant-like particle cholesterol for the low collateralization was 0.696, with a cut-off value of 0.485, and its sensitivity was 82.88%. Besides, the addition of the estimated remnant-like particle cholesterol into the baseline model consisting of traditional risk factors could improve the incremental value of the discrimination of impaired collateralization only in overall and type 2 diabetes mellitus populations. Conclusions: The increased estimated remnant-like particle cholesterol is independently associated with impaired collateralization in patients with coronary chronic total occlusion lesions. Therapies targeting at remnant-like particle cholesterol may be needed in advanced coronary artery disease patients with type 2 diabetes mellitus not suitable for vascular revascularization.

An issue with cardiac ventilation can result in death at any moment throughout a persons life. The apnea-hypopnea index (AHI) has historically been influenced by medical ventilation on heart failure; nevertheless, the sleep snore analysis is the best model to diagnose. The problems with ventilation are caused by problems with air pressure and blood circulation in the heart valves, where the pathological measures are continually detecting ventilation issues. Understanding the pathophysiology of OSA will have a direct impact on clinical treatment choices as well as the design of clinical studies. Treatments could be tailored to each patient's unique needs based on the fundamental reason to their OSA. Through the OSA treatment, patients could feel better, and understanding OSA symptoms and also outcomes will improve patients health; as a result, the study reveals that most of the population are likely to benefit from specific OSA treatment approaches. For achieving the benefits of OSA treatment the classification accuracy is needed to be improved. So, in this research work, an LeNet-100 CNN-based deep learning technology is used to get information and apply the classification approaches. We obtained the heart failure dataset from the Kaggle website for conducting a meta-analysis. An accuracy of 93.25, sensitivity of 97.29, recall of 96.34, and F measure of 95.34 had been attained. This approach outperforms the technology and is comparable to the present heart failure meta-analysis..

Aim. To explore the association between the serum C1q/tumor necrosis factor‐related protein 9 (CTRP9) and the formation of coronary collateral circulation in obstructive coronary artery disease (CAD). Methods. A total of 206 patients who underwent coronary angiography at Beijing Anzhen Hospital and had epicardial arteries with at least 95% stenotic lesion were enrolled. Blood samples were taken after an overnight fasting before the coronary angiography. Serum CTRP9 level was measured using commercial enzyme linked immunosorbent assay (ELISA) kit. The development of coronary collateralization was determined according to the Rentrop classification system. Rentrop score 0‐1 was graded as impaired or less‐developed coronary collateralization (n = 54) while the Rentrop score 2‐3 was defined as well‐developed collateralization (n = 152). Results. Serum CTRP9 level was significantly higher in well‐developed collateralization and diabetes groups (P < 0.001). To further explore the association between the CTRP9 level and coronary collateralization, the enrolled participants were divided into 3 tertiles according to the serum CTRP9 level. The prevalence of impaired coronary collateralization decreased stepwise with the increasing CTRP9 tertiles (P for trend P = 0.046). Conclusions. Serum CTRP9 reflects well‐developed coronary collateralization in nondiabetic patients with obstructive CAD, and CTRP9 level ≥ 1.217 indicated a greater chance to forming well‐developed coronary collaterals.

Introduction: In-stent restenosis (ISR) remains a challenging issue despite the great advance of drug-eluting stents (DES). In addition, the consensus was lacking regarding the optimal strategy for DES-ISR. Therefore, we aimed to evaluate angiographic and clinical outcomes of the two most effective treatments DES vs. drug-eluting balloon (DCB) for patients with DES-ISR.Methods: This meta-analysis used the data from the randomized controlled trials (RCTs), which were identified by a systematic search in the databases of PubMed, Embase, and Cochrane Library. Target lesion revascularization (TLR) was regarded as the primary endpoint. In addition, the late angiographic outcomes and other clinical outcomes, namely, cardiac death, myocardial infarction (MI), target vessel revascularization, stent thrombosis, and major adverse cardiac events, were also included for analysis.Results: Five RCTs with about 1,193 patients were included in this meta-analysis for the analysis. For the primary endpoint, the overall pooled outcomes suggested repeat DES implantation was associated with a significant reduction in the term of TLR compared with DCB angioplasty (risk ratio = 1.53, 95% CI 1.15–2.04, p = 0.003). But no significant difference in angiographic outcomes and other clinical endpoints were observed between DES and DCB. In the subgroup analysis, DCB was inferior to new-generation DES (NG-DES)/everolimus-eluting stent (EES) in the term of TLR. In addition, this non-significant trend was also noted in the subgroup of the paclitaxel-eluting stent (PES) vs. DCB. For the angiographic endpoints, EES, not PES, was associated with larger minimum lumen diameter [mean difference (MD) = −0.25, 95% CI −0.38 to −0.11, p = 0.0003], lower percent diameter stenosis (MD = 7.29%, 95% CI 2.86–11.71%, p = 0.001), and less binary restenosis (OR = 2.20, 95% CI 1.18–4.11, p = 0.01). But NG-DES/EES was comparable to DCB in cardiac death, MI, and stent thrombosis.Conclusions: For the patients with DES-ISR, treatment with DES, especially NG-DES/EES could reduce the risk of TLR significantly compared to DCB at long-term follow-up.

Recent studies have substantiated the role of the triglyceride glucose (TyG) index in predicting the prognosis of coronary artery disease (CAD) patients, while no relevant studies have revealed the association between the TyG index and coronary collateralization in the event of coronary chronic total occlusion (CTO). The current study intends to explore whether, or to what extent, the TyG index is associated with impaired collateralization in CAD patients with CTO lesions. The study enrolled 1093 CAD patients undergoing cardiac catheterization for at least one CTO lesion. Data were collected from the Beijing Anzhen Hospital record system. The degree of collaterals was determined according to the Rentrop classification system. The correlation between the TyG index and coronary collateralization was assessed. Overall, 318 patients were included in a less developed collateralization (Rentrop classification 0-1) group. The TyG index was significantly higher in patients with impaired collateralization (9.3±0.65 vs. 8.8±0.53, PP<0.001). In addition, subgroup analysis showed that higher TyG index values remained strongly associated with increased risk of less developed collateralization. To compare the risk assessment efficacy for the formation of collateralization between the TyG index and other metabolic abnormality indicators, an area under the receiver-operating characteristic (ROC) curve (AUC) was obtained. A significant improvement in the risk assessment performance for impaired collateralization emerged when adding the TyG index into a baseline model. The increased TyG index is strongly associated with less developed collateralization in CAD patients with CTO lesions and its risk assessment performance is better than single metabolic abnormality indicators.

Background: The prevalence of coronary artery disease (CAD) continues to increase among young Chinese adults. Current smoking has been recognized as a major risk factor for premature CAD, and hyperhomocysteinaemia (HHcy) has also been suggested to be associated with CAD progression. However, the combined effect of current smoking and HHcy on the severity of coronary artery stenosis in young adults is still uncertain. Methods: We consecutively collected young patients (18–35 years of age), diagnosed with CAD and underwent coronary angiography (CAG) at Anzhen Hospital between January 2013 and May 2020. HHcy was defined as serum homocysteine (Hcy) level > 15 µmol/L. The severity of coronary artery stenosis was evaluated by Gensini Score. The co-effect of current smoking and HHcy on CAD severity as well as the relationship between plasma Hcy, pack-years of smoking and CAD severity were assessed by multivariate linear regression analysis. Results: A total of 989 participants (mean age, 33 years; 96.2% male) fulfilling the criteria were enrolled in this study. Patients with both HHcy and current smoking accounted for 39.1% of all the subjects. Multivariate liner analysis indicated both serum Hcy levels (β 0.302; 95% CI 0.141–0.462; P < 0.001) and pack-years of smoking (β 0.523; 95% CI 0.265–0.781; P < 0.001) were independently associated with the severity of coronary artery stenosis after adjusting for other traditional confounders. In addition, serum Hcy levels were correlated with pack-years of smoking in young CAD patients (r = 0.116, P = 0.001). Moreover, combination of HHcy and current smoking was suggested to have higher risk for CAD severity (β 17.892; 95% CI 11.314–24.469; P < 0.001), compared with HHcy (β 7.471; 95% CI 0.009–14.934; P = 0.048) or current smoking (β 7.421; 95% CI 0.608–14.233; P = 0.033) alone. Conclusion: Combination of HHcy and smoking is independently associated with the severity of CAD in young patients ≤ 35 years of age.

Aim: Recently, the atherogenic index of plasma (AIP) has been proposed as a novel, reliable plasma atherogenicity marker. This study aimed to investigate the association of AIP with the risk of in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS). Methods: This study retrospectively enrolled patients with ACS followed by angiography within 6 to 18 months after successful percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). And the participants were divided into ISR or non-ISR groups based on the angiographic follow-up results. AIP was defined as the base 10 logarithm of the ratio of serum triglyceride (mmol/L) to high-density lipoprotein cholesterol (mmol/L). Results: This study recruited 1319 patients with ACS, 199 of which had ISR. Compared with the non-ISR group, patients in the ISR group had higher level of AIP (0.199±0.290 vs 0.131±0.282, p=0.002). In the multiple logistic regression analysis, AIP was an independent risk factor for DES-ISR (OR=2.100, 95% CI 1.134 to 3.891, p=0.018). When we modulated AIP as a categorical variable, the risk of DES-ISR increased in quartile 4 compared to quartile 1 (OR=1.713, 95% CI 1.040 to 2.822, p=0.034). Furthermore, this association remains stable in various subgroups. Unexpectedly, the subgroup analysis suggested AIP and DES-ISR had a stronger positive association in individuals with low-density lipoprotein cholesterol (LDL-C) ＜1.8 mmol/L. Conclusions: AIP and the risk of DES-ISR were positively and independently correlated in patients with ACS, especially in those with an LDL-C ＜1.8 mmol/L.

Background: Recent studies have substantiated the role of triglyceride glucose index (TyG index) in the prognosis of coronary artery disease (CAD) patients while no relevant studies revealed the association between TyG index and coronary collateral circulation (CCC) in the event of coronary chronic total occlusion (CTO). Our study intends to explore whether or to what extent TyG index is associated with less developed CCC in CAD patients with CTO lesions.Methods: The study enrolled 1093 ACS patients undergoing percutaneous coronary intervention (PCI) for at least one CTO lesion. Relevant data was collected from Beijing Anzhen Hospital record system. The degree of collaterals was determined according to Rentrop classification system. The correlation between TyG index and coronary collateralization was assessed.Results: Overall, 318 patients were divided into poor CCC group. TyG index was significantly higher in patients with poor CCC (9.3±0.65 vs. 8.8±0.53, P＜0.001). After adjusting for various confounding factors, TyG index remained to be correlated with the occurrence of poor CCC, with an ORs (95% CIs) of 1.59 (1.07-2.36) in T2 group and 5.72 (3.83-8.54) in T3 group compared with the first tertile. Besides, subgroup analysis showed that higher TyG index values remained to be strongly associated with increased risks of poor CCC. Lastly, to compare the risk assessment efficacy for the formation of CCC between TyG index and glycosylated hemoglobin A1c (HbA1c) and another insulin resistance (IR) surrogate marker triglyceride-to-high-density lipoprotein cholesterol ratio, area under the receiver-operating characteristic (ROC) curve (AUC) was obtained, a significant improvement on the risk assessment performance for the poor CCC emerged when adding TyG index into a baseline model [AUC, 0.629 for baseline model vs. 0.724 for baseline model + TyG index vs. 0.638 for baseline model +HbA1c vs. 0.721 for baseline model +TG/HDL-C, PConclusions: The TyG index is strongly associated with the occurrence of poor CCC in CAD patients with CTO lesions and its risk assessment performance is better than HbA1c and TG-to-HDL-C ratio.

Background: Accumulating evidence demonstrates that perivascular adipose tissue (PVAT) plays an important role in maintaining vascular homeostasis. The formation of macrophage foam cells is a central feature of atherosclerosis. This study aimed to evaluate the effect of PVAT-derived exosomes (EXOs) on the lipid accumulation of macrophages and verify the anti-atherogenic characteristics of PVAT.Methods and Results: We extracted EXOs from the PVAT and subcutaneous adipose tissue (SCAT) of wild-type C57BL/6J mice. After coincubation, the EXOs were taken up by RAW264.7 cells. Oil Red O staining revealed that macrophage foam cell formation and intracellular lipid accumulation were ameliorated by PVAT-EXOs. Flow cytometry showed that PVAT-EXOs significantly reduced macrophage uptake of fluorescence-labelled oxidised low-density lipoprotein (ox-LDL). In addition, high-density lipoprotein-induced cholesterol efflux was promoted by PVAT-EXOs. Western blot analysis showed the downregulation of macrophage scavenger receptor A and the upregulation of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1, which could be mediated by the overexpression of peroxisome proliferator-activated receptor γ and was independent of liver X receptor α.Conclusion: Our findings suggest that PVAT-EXOs reduce macrophage foam cell formation by regulating the expression of cholesterol transport proteins, which provides a novel mechanism by which PVAT protects the vasculature from atherosclerosis.