Comparison of revascularization with conservative medical treatment in maintenance dialysis patient with coronary artery disease: a systemic review and meta-analysis.

Background: The primary cause of death among maintenance dialysis patients is coronary artery disease (CAD). However, the best treatment plan has not yet been identified. Methods: The relevant articles were retrieved from various online databases and references from their inception to October 12, 2022. The studies that compared revascularization [percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] with medical treatment (MT) among maintenance dialysis patients with CAD were selected. The outcomes evaluated were long-term (with a follow-up of at least 1 year) all-cause mortality, long-term cardiac mortality, and the incidence rate of bleeding events. Bleeding events are defined according to TIMI hemorrhage criteria: (1) major hemorrhage, intracranial hemorrhage or clinically visible hemorrhage (including imaging diagnosis) with decrease of hemoglobin concentration ≥5 g/dl; (2) minor hemorrhage, clinically visible bleeding (including imaging diagnosis) with a drop in hemoglobin of 3-5 g/dl; (3) minimal hemorrhage, clinically visible bleeding with hemoglobin drop <3 g/dl. In addition, revascularization strategy, CAD type, and the number of diseased vessels were considered in subgroup analyses. Results: A total of eight studies with 1,685 patients were selected for this meta-analysis. The current findings suggested that revascularization was associated with low long-term all-cause mortality and long-term cardiac mortality but a similar incidence rate of bleeding events compared to MT. However, subgroup analyses indicated that PCI is linked to decreased long-term all-cause mortality compared to MT but CABG did not significantly differ from MT in terms of long-term all-cause mortality. Revascularization also showed lower long-term all-cause mortality compared to MT among patients with stable CAD, single-vessel disease, and multivessel disease but did not reduce long-term all-cause mortality among patients with ACS. Conclusion: Long-term all-cause mortality and long-term cardiac mortality were reduced by revascularization in comparison to MT alone in patients undergoing dialysis. Larger randomized studies are needed to confirm the conclusion of this meta-analysis.

Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE-/- Mice.

Background: Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to antigens, including oxidized low-density lipoprotein (oxLDL) and phosphorylcholine (PC). Dendritic cells (DCs), which are antigen-presenting cells that activate T cells, are present in atherosclerotic lesions and are activated in immune organs. However, the mechanism by which PC promotes atherosclerosis is unclear. Methods and Results: To evaluate whether PC promotes atherosclerosis via DCs, 2×105 DCs activated by PC-keyhole limpet hemocyanin (DCs+PC-KLH) were injected into ApoE-/- mice and the features of the plaques and the effects of the DCs on cellular and humoral immunity against PC-KLH were determined. Mice injected with DCs+PC-KLH had significantly larger atherosclerotic lesions than controls, with increased inflammation in the lesions and plaque instability. Furthermore, DCs+PC-KLH were characterized using flow cytometry after coculture of bone marrow-derived DCs and naïve T cells. DCs+PC-KLH showed an inflammatory phenotype, with increased CD86, CD40, and major histocompatibility complex Class II molecules (MHC-II), which promoted PC-specific T helper (Th) 1 and Th17 cell differentiation in vivo and in vitro. Moreover, 2 weeks after the administration of DCs+PC-KLH to mice, these mice produced PC- and oxLDL-specific IgG2a, compared with no production in the controls. Conclusions: These findings suggest that DCs presenting PC promote specific immunity to PC, increase lesion inflammation, and accelerate atherosclerosis, which may explain how PC promotes atherosclerosis.

[Impact of sperm DNA fragmentation on the outcome of frozen-thawed blastocyst transfer in in vitro fertilization and embryo transfer].

OBJECTIVE: To study the impact of sperm DNA fragmentation (DF) on the outcome of frozen-thawed blastocyst transfer in in vitro fertilization and embryo transfer (IVF-ET). METHODS: We retrospectively analyzed 308 cases of routine IVF-ET performed at our Center of Reproductive Medicine from January 2016 to January 2018. According to the sperm DNA fragmentation index (DFI), we divided the patients into a normal DFI (DFI ≤ 15%, n = 114), a moderate DFI (15% < DFI ≤ 30%, n = 103), and a high DFI group (DFI > 30 %, n = 91), and compared the development of embryos and clinical outcomes among the three groups. RESULTS: The blastocyst formation rate was remarkably higher in the normal and moderate DFI groups than in the high DFI group (68.9% and 66.2% vs 58.3%, P < 0.05) but the percentage of available blastocysts exhibited no statistically significant difference between the former two and the latter group (88.1% and 84.0% vs 81.2%, P > 0.05). There were statistically significant differences among the normal, moderate and high DFI groups in the percentage of high-quality blastocysts (80.3% vs 68.8% vs 59.7%, P < 0.05). The implantation rate was dramatically lower in the high DFI group than in the normal and moderate DFI groups (30.4% vs 43.1% and 41.0%, P < 0.05), and so was the clinical pregnancy rate (33.6% vs 43.2% and 40.2%, P < 0.05), but the abortion rate markedly higher in the former than in the latter two groups (16.2% vs 10.0% and 9.8%, P < 0.05). CONCLUSIONS: High sperm DFI can not only significantly reduce the rates of blastocyst formation, available blastocysts and high-quality blastocysts, but also decrease the rates of implantation and clinical pregnancy and increase that of abortion after frozen-thawed blastocyst transfer.

Down-regulation and Clinical Implication of Galectin-9 Levels in Patients with Acute Coronary Syndrome and Chronic Kidney Disease.

In various autoimmune diseases, Galecin-9 (Gal-9) has been shown to regulate the T-cell balance by decreasing Th1 and Th17, while increasing the number of regulatory T cells (Tregs). However, the role of Gal-9 in the patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) remains unclear. This study aims to measure the Gal-9 levels in serum and peripheral blood mononuclear cells (PBMCs) in patients with ACS plus CKD and examine their clinical implication. The serum levels of Gal-9 were determined by enzyme-linked immunosorbent assay (ELISA), the expression levels of Gal-9, Tim-3, and Foxp3 mRNA in PBMCs were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the expression of Gal-9 on the surface of PBMCs and in PBMCs was analyzed by flow cytometry. Furthermore, the correlation of serum Gal-9 levels with anthropometric and biochemical variables in patients with ACS plus CKD was analyzed. The lowest levels of Gal-9 in serum and PBMCs were found in the only ACS group, followed by the ACS+CKD group, and the normal coronary artery (NCA) group, respectively. Serum Gal-9 levels were increased along with the progression of glomerular filtration rate (GFR) categories of G1 to G4. Additionally, serum Gal-9 levels were negatively correlated with high-sensitivity C-reactive protein (hs-CRP), estimated GFR (eGFR), and lipoprotein(a), but positively with creatinine, age, osmotic pressure, and blood urea nitrogen (BUN). Notably, serum Gal-9 was independently associated with hs-CRP, osmotic pressure, and lipoprotein(a). Furthermore, serum Gal-9 levels were elevated in patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT) in ACS group. It was suggested that the levels of Gal-9 in serum and PBMCs were decreased in patients with simple ACS and those with ACS plus CKD, and hs-CRP, eGFR, osmotic pressure and T2DM may have an influence on serum Gal-9 levels.

The Long Noncoding RNA Hotair Regulates Oxidative Stress and Cardiac Myocyte Apoptosis during Ischemia-Reperfusion Injury.

Oxidative stress and subsequent cardiac myocyte apoptosis play central roles in the initiation and progression of myocardial ischemia-reperfusion (I/R) injury. Homeobox transcript antisense intergenic RNA (Hotair) was previously implicated in various heart diseases, yet its role in myocardial I/R injury has not been clearly demonstrated. Mice with cardiac-restricted knockdown or overexpression of Hotair were exposed to I/R surgery. H9c2 cells were cultured and subjected to hypoxia/reoxygenation (H/R) stimulation to further verify the role and underlying mechanisms of Hotair in vitro. Histological examination, molecular detection, and functional parameters were determined in vivo and in vitro. In response to I/R or H/R treatment, Hotair expression was increased in a bromodomain-containing protein 4-dependent manner. Cardiac-restricted knockdown of Hotair exacerbated, whereas Hotair overexpression prevented I/R-induced oxidative stress, cardiac myocyte apoptosis, and cardiac dysfunction. Mechanistically, we observed that Hotair exerted its beneficial effects via activating AMP-activated protein kinase alpha (AMPKα). Further detection revealed that Hotair activated AMPKα through regulating the enhancer of zeste homolog 2/microRNA-451/calcium-binding protein 39 (EZH2/miR-451/Cab39) axis. We provide the evidence that endogenous lncRNA Hotair is an essential negative regulator for oxidative stress and cardiac myocyte apoptosis in myocardial I/R injury, which is dependent on AMPKα activation via the EZH2/miR-451/Cab39 axis.

Plasma oxidized high-density lipoprotein and glycated apolipoprotein A-I concentrations in ST-segment elevation myocardial infarction patients with stress hyperglycaemia or high thrombus burden.

BACKGROUND: High-density lipoprotein (HDL) particles exert many beneficial actions that may help protect against cardiovascular disease. However, recent work has demonstrated that HDL can be oxidized and glycated under certain circumstances and may become pro-atherogenic. The present study investigated the impact of oxidized high-density lipoprotein (ox-HDL) and glycated apolipoprotein A-I (gly-ApoA-I) in patients presenting with ST-elevation myocardial infarction (STEMI). METHODS: We assessed 55 consecutive patients with STEMI. Patients were divided into: (1) a stress hyperglycaemia (SH) and a no SH group; and (2) a high thrombus burden (HTB) group and a low thrombus burden (LTB) group. Meanwhile, 48 healthy volunteers were recruited as controls. Plasma ox-HDL and gly-ApoA-I concentrations were measured on admission and 7 days after admission. RESULTS: Higher concentrations of ox-HDL and gly-ApoA-I were found in the STEMI group than in the control group on admission and at d7. Further subgroup analysis showed that ox-HDL and gly-ApoA-I were higher in the SH group than in the no SH group at both time points; the HTB group had higher ox-HDL and ox-HDL/HDL-C levels than the LTB group on admission and at d7. However, gly-ApoA-I and the relative intensity of ApoA-I glycation showed no significant differences between the HTB and LTB groups. CONCLUSIONS: The present data indicate that: (1) SH is associated with increased plasma concentrations of ox-HDL and gly-ApoA-I and therefore aggressive treatment is recommended; and (2) that ox-HDL and ox-HDL/HDL-C were higher in the HTB group and may be used to quantify thrombus burden.

Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.

OBJECTIVE: CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4(+)LAP(+) Tregs are defective in ACS. METHODS: One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4(+)LAP(+) Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4(+) T cells were determined by flow cytometry. The function of CD4(+)LAP(+) Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-ß protein (TGF-ß) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction. RESULTS: We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+) T cells and the serum levels of TGF-ß in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts. CONCLUSIONS: A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

Overexpression of CXCL16 promotes a vulnerable plaque phenotype in Apolipoprotein E-Knockout Mice.

BACKGROUND: CXCL16 has been shown to be involved in atherosclerotic lesion development, but its role in preexisting lesions is still unclear. This study aims to assess the effect of CXCL16 on the stability of preexisting lesions. METHODS: We firstly measured plasma CXCL16 level in Apolipoprotein E-Knockout (ApoE KO) mice with either high-cholesterol diet (HCD) or normal diet (ND) by enzyme-linked immunosorbent assay (ELISA). Then, silastic collars were placed around the carotid arteries in HCD-ApoE KO mice to accelerate atherosclerotic lesions. Five weeks later, CXCL16 was overexpressed by intravenous injection of lentivirus carrying CXCL16 transgene. Two weeks after infection, lesions were stained with hematoxylin and eosin (HE) and with oil red O. Biomarkers in the lesions, such as MMPs, CCL2, VCAM-1 and TNF-α were measured by real-time polymerase chain reaction (RT-PCR), which indicate the instability of plaques. RESULTS: The level of CXCL16 in plasma was higher in HCD-ApoE KO mice as compared to ND-ApoE KO mice. Circulating CXCL16 overexpression does not affect the size of preexisting plaques, but it leads to vulnerable plaque morphology and increases the expression of markers of plaque destabilization. CONCLUSION: Systemic CXCL16 becomes much higher in atherosclerosis, and it could be a potential atherogenic biomarker. Overexpression of CXCL16 promotes the evolution of preexisting lesions to vulnerable plaques in ApoE KO mice.