EHD1 impaired decidualization of endometrial stromal cells in recurrent implantation failure: role of SENP1 in modulating progesterone receptor signalling†.

Recurrent implantation failure (RIF) patients exhibit poor endometrial receptivity and abnormal decidualization with reduced effectiveness and exposure to progesterone, which is an intractable clinical problem. However, the associated molecular mechanisms remain elusive. We found that EH domain containing 1 (EHD1) expression was abnormally elevated in RIF and linked to aberrant endometrial decidualization. Here we show that EHD1 overexpressed in human endometrial stromal cells significantly inhibited progesterone receptor (PGR) transcriptional activity and the responsiveness to progesterone. No significant changes were observed in PGR mRNA levels, while a significant decrease in progesterone receptor B (PRB) protein level. Indeed, EHD1 binds to the PRB protein, with the K388 site crucial for this interaction. Overexpression of EHD1 promotes the SUMOylation and ubiquitination of PRB, leading to the degradation of the PRB protein. Supplementation with the de-SUMOylated protease SENP1 ameliorated EHD1-repressed PRB transcriptional activity. To establish a functional link between EHD1 and the PGR signalling pathway, sg-EHD1 were utilized to suppress EHD1 expression in HESCs from RIF patients. A significant increase in the expression of prolactin and insulin-like growth factor-binding protein 1 was detected by interfering with the EHD1. In conclusion, we demonstrated that abnormally high expression of EHD1 in endometrial stromal cells attenuated the activity of PRB associated with progesterone resistance in a subset of women with RIF.

In vivo predictors of plaque erosion in patients with ST-segment elevation myocardial infarction: a clinical, angiographical, and intravascular optical coherence tomography study.

Aims: Plaque erosion is a significant substrate of acute coronary thrombosis. This study sought to determine in vivo predictors of plaque erosion in patients with ST-segment elevation myocardial infarction (STEMI). Methods and results: A prospective series of 822 STEMI patients underwent pre-intervention optical coherence tomography. Using established diagnostic criteria, 209 had plaque erosion (25.4%) and 564 had plaque rupture (68.6%). Plaque erosion was more frequent in women <50 years when compared with those ≥50 years of age (P = 0.009). There was a similar, but less striking, trend in men (P = 0.011). Patients with plaque erosion were more frequently current smokers but had fewer other coronary risk factors (dyslipidaemia, hypertension, chronic kidney disease, and diabetes mellitus) than those with plaque rupture. There was a preponderance of plaque erosion in the left anterior descending artery (LAD; 61.2%), whereas plaque rupture was more equally distributed in both the LAD (47.0%) and right coronary artery (43.3%). Despite the similar spatial distribution of erosions and ruptures over the lengths of the coronary arteries, plaque erosion occurred more frequently near a bifurcation (P < 0.001). In the multivariable analysis, age <50 years, current smoking, absence of other coronary risk factors, lack of multi-vessel disease, reduced lesion severity, larger vessel size, and nearby bifurcation were significantly associated with plaque erosion. Nearby bifurcation and current smoking were especially notable in men, while age <50 years was most predictive in women. Conclusions: Plaque erosion was a predictable clinical entity distinct from plaque rupture in STEMI patients, and gender-specific role of risk factors in plaque erosion should be considered.

Plaque erosion delays vascular healing after drug eluting stent implantation in patients with acute coronary syndrome: An In Vivo Optical Coherence Tomography Study.

OBJECTIVES: To compare vascular healing after drug-eluting stent (DES) implantation between plaque rupture (PR) and plaque erosion (PE). BACKGROUND: Vascular response after stent implantation in patients with PR has been extensively studied. Little is known about vascular healing after stent implantation in PE. METHODS: Sixty-five ACS patients who received optical coherence tomography (OCT) imaging of the culprit lesions both before and after stent implantation at baseline as well as at 6 months were included in this study. Patients were divided into two groups: PR (n = 19) and PE (n = 24). Prestent thrombus burden and poststent intrastent structure (ISS) volume were analyzed during the index procedure. The ratio of uncovered to total stent struts per cross-section score (RUTTS) and neointimal thickness and area were measured at follow-up. RESULTS: OCT imaging showed that compared with PR, PE showed a significantly lower prestent thrombus score (34.2 ± 19.2 vs. 68.6 ± 44.2, P = 0.009) at baseline and a smaller poststent ISS volume (0.7 ± 0.9 mm3 vs. 2.1 ± 1.9 mm3 , P = 0.019). At the 6-month follow-up, PE showed a higher incidence of RUTTS >0.3 (12.2 ± 14.4 vs. 2.0 ± 4.5%, P = 0.003), thinner neointimal thickness (0.05 ± 0.02 mm vs. 0.12 ± 0.08 mm, P = 0.002), and smaller neointimal area (0.5 ± 0.2 vs. 1.2 ± 0.9 mm2 , P = 0.004) compared with PR. In a multivariate logistic model, PE was identified as an independent predictor for RUTTS >0.3. CONCLUSIONS: PE was associated with less favorable healing following DES implantation when compared to PR at 6 months, indicating longer dual-antiplatelet therapy may be necessary for patients with PE. © 2017 Wiley Periodicals, Inc.

Chronic total occlusion is associated with a higher incidence of malapposition and uncovered stent struts: OCT findings at 6 months following DES implantation.

OBJECTIVES: To compare stent coverage and malapposition in patients with chronic total occlusion (CTO) lesions and non-CTO lesions (including lipid-rich plaque [LRP] and non-lipid-rich plaque [non-LRP]) after drug-eluting stent (DES) implantation by optical coherence tomography (OCT). BACKGROUND: Different initial lesion characteristics may be related to heterogeneous vessel responses after DES implantation. However, the vessel response in patients with CTO and non-CTO lesions after stenting is unclear. Methods We retrospectively enrolled 64 patients with 68 target lesions. All of the patients underwent OCT imaging immediate after stenting and 6 months after stenting. LRP was defined as the plaque with lipid content in ≥2 quadrants. Non-LRP consisted of fibrous, fibrocalcific plaque, and lipid plaque with less than 2 quadrants lipid content. RESULTS: The malapposition (3.0%, 2.6% vs. 0.6%, P = 0.022), tissue protrusion (15.0% vs. 11.0% vs. 6.4%, P < 0.001), and intrastent thrombus (3.8% vs. 2.4% vs. 1.1%, P = 0.012) were more frequent in the CTO and LRP groups. At 6-month follow-up, malapposition (5.0% vs. 1.0% and 0.4%, P = 0.002) and cross sections with uncovered struts (23.4% vs. 8.2% and 6.6%, P < 0.001) were most frequently observed in the CTO group. Although the incidence of stent thrombosis was non-significantly higher in the CTO group than the other two groups, no events were observed in patients with CTO. CONCLUSIONS: Patients with CTO lesions showed unfavorable responses to DES in the acute phase as well as at the 6-month follow-up, indicating the important pathological link between the original lesion morphology underneath the stents and heterogeneous artery healing. © 2017 Wiley Periodicals, Inc.

Processing Stage-Induced Formation of Advanced Glycation End Products in Cooked Sausages with the Addition of Spices.

This study aims to evaluate the relationship between the four processing stages of cooked sausage preparation (raw, drying, baking, and steaming) and the formation of advanced glycation end products (AGEs), 1,2-dicarbonyl compounds, and lipid and protein oxidation in sausages with spices. Baking and steaming significantly promoted lipid and protein oxidation. The Nε-carboxymethyllysine (CML) content increased from 4.32-4.81 µg/g in raw samples to 10.68-16.20 µg/g in the steamed sausages. Nε-carboxyethyllysine (CEL) concentrations increased by approximately 1.7-3.7 times after steaming. The methylglyoxal concentration increased dramatically after baking and then rapidly decreased in the steaming stage. Chili promoted the formation of CML and CEL. The CEL concentration increased in samples containing garlic, but yellow mustard and garlic slightly reduced CML concentrations in the cooked sausages. The spices decreased the lipid and protein stability of the cooked sausages, increasing malondialdehyde and protein carbonyls. Lipid oxidation and 3-deoxyglucosone positively correlated with CML and CEL levels. Black pepper had no impact on CML when the sausages were baked but remarkably increased the content of both CML and CEL in the steaming stage. Thus, the impact of spices on sausages depends on both the specific spices used and the category of AGEs formed.

Association of ABO blood groups and non-culprit plaque characteristics in acute coronary syndrome: an optical coherence tomography study.

BACKGROUND: Cardiovascular disease (CVD) poses a serious threat to human health. Research shows that ABO blood groups, especially non-O blood types, are closely related to the incidence of cardiovascular diseases (CVDs). This study aimed to determine the associations of blood types with non-culprit coronary plaque characteristics using optical coherence tomography (OCT). METHODS: A total of 257 acute coronary syndrome (ACS) patients (average age, 59.39±10.08 years, 80% male) who underwent OCT of 3 vessels were identified. Subjects were divided into 2 groups: the O blood group (71 patients with 121 plaques) and the non-O group (186 patients with 329 plaques). The non-culprit coronary plaque features of the two groups were compared using OCT. RESULTS: The non-type O group had larger lipid arcs, thinner fibrous caps, and a greater number of thin-cap fibro atheromas (TCFAs). The type A, B, and AB blood groups had larger lipid arcs than the type O blood group, as well as thinner fibrous caps and more TCFAs. The type A blood group had thinner fibrous caps and a greater number of TCFAs than the type B and AB blood groups. CONCLUSIONS: ACS patients with type non-O blood had more non-culprit plaques. Patients with type A blood, in particular, had more vulnerable characteristics than those with type O blood.

Preliminary functional inquiry of lncRNA ENST00000433673 in embryo implantation using bioinformatics analysis.

Long non-coding RNAs (lncRNAs), a class of non-coding RNA, have been shown to be essential in many diseases, such as infertility. Here, we found three candidate lncRNAs, ENST00000414116, ENST00000433673, and ENST00000448179, that are highly expressed in the uterus endometrial tissues of normal patients compared to the tissues of patients with adenomyosis, endometriosis, and recurrent implantation failure. lncRNAs ENST00000414116 and ENST00000433673 showed high expression in endometrial stromal cells (ESCs) and endometrial epithelial cells (EECs), respectively, and lncRNA ENST00000448179 was specifically expressed in ESCs. The bioinformatics analysis results indicated that the target mRNAs of lncRNA ENST00000433673 were related to biological adhesion. Interestingly, intercellular adhesion molecule 1 (ICAM1), an interacting mRNA of the target mRNA integrin subunit alpha L (ITGAL), has been reported be an important regulator of embryo implantation. Further studies found that the target mRNA ITGAL and the interacting mRNA ICAM1 were highly expressed in the uterus endometrial tissues and EECs of normal patients. Based on our results, our study indicates that lncRNA ENST00000433673 might mediate the high expression of the target mRNA ITGAL, thereby promoting the expression of the interacting mRNA ICAM1 and the adhesion of EECs, which facilitates adhesion and implantation between the embryo and the mater. Abbreviations: AMs: adenomyosis; EMs: endometriosis; RIF: recurrent implantation failure; miRNAs: microRNAs; lncRNAs: Long non-coding RNAs; RT-qPCR: real-time quantitative PCR; ESCs: endometrial stromal cells; EECs: endometrial epithelial cells; BFE: free binding energy; PCDHB9: protocadherin beta 9; PARVG: parvin gamma; MAPK6: mitogen-activated protein kinase 6; LAF1: lymphocyte function-associated antigen 1.

Chronic kidney disease predicts coronary plaque vulnerability: an optical coherence tomography study.

OBJECTIVE: The addition of cystatin C to creatinine in calculating the estimated glomerular filtration rate (eGFR) is known to improve the risk prediction for cardiovascular events. We sought to investigate the associations between eGFRs calculated by three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and coronary plaque phenotype by optical coherence tomography. PATIENTS AND METHODS: We analyzed 181 nonculprit plaques from 116 coronary artery disease patients. For each patient, the eGFR was calculated using the CKD-EPIcreatinine, CKD-EPIcystatin C, and CKD-EPIcombination equations. Patients were divided into three categories according to the eGFR calculated by each equation (≥90, 60-89, and <60 ml/min/1.73 m). RESULTS: The prevalence of thin-cap fibroatheroma (TCFA) was correlated inversely with eGFR calculated using CKD-EPIcystatin C and CKD-EPIcombination equations, but not using the CKD-EPIcreatinine equation. The best cut-off values of eGFR calculated by these two equations for differentiating TCFA were 83 and 84 ml/min/1.73 m, respectively. Compared with the CKD-EPIcreatinine equation, patients who were reclassified upward or downward categories by the CKD-EPIcystatin C equation were associated with consistently lower [adjusted odds ratio=0.27, 95% confidence interval (CI), 0.08-0.86] and higher (adjusted odds ratio=2.41, 95% CI, 1.08-5.41) prevalence for TCFA, respectively. The net reclassification improvement with cystatin C, compared with creatinine, was 0.45 (95% CI, 0.20-0.69) for TCFA, 0.38 (95% CI, 0.09-0.67) for thrombus, and 0.21 (95% CI, 0.00-0.42) for cholesterol crystals. Results were generally similar for the CKD-EPIcombination equation. CONCLUSION: The use of cystatin C alone or in combination with creatinine, compared with creatinine alone, for GFR estimation strengthens the associations between the eGFR and prevalence of vulnerable plaque characteristics.

Culprit plaque characteristics in women vs men with a first ST-segment elevation myocardial infarction: In vivo optical coherence tomography insights.

BACKGROUND: It is unclear whether more severe coronary atherosclerosis is a prerequisite to an initial acute coronary event in women vs men. HYPOTHESIS: Women may have more severe coronary atherosclerosis than men in patients with acute coronary event. METHODS: We used intravascular optical coherence tomography (OCT) to evaluate gender differences in culprit-plaque morphology in patients with a first ST-segment elevation myocardial infarction (STEMI).We retrospectively enrolled 211 consecutive patients who experienced a first STEMI and underwent an OCT examination of their infarct-related artery before primary percutaneous coronary intervention. RESULTS: Of the 211 patients enrolled, 162 (76.7%) were men and 49 (23.2%) were women. The women were significantly older than the men (mean age, 60.2 ± 8.2 vs 55.7 ± 11.2 years; P = 0.01) and less likely to be current smokers (P = 0.02). Moreover, the delay from symptom onset to reperfusion was longer in women than in men (7.6 ± 6.1 vs 5.5 ± 4.4 hours; P = 0.01). The OCT data indicated that there were no gender differences in culprit-plaque morphology, including lipid length, lipid arc, minimum fibrous cap thickness, or minimum lumen area. Additionally, no gender differences were found in the prevalence of plaque rupture, thin-cap fibroatheroma, residual thrombus, microvessels, macrophages, cholesterol crystals, or calcification. CONCLUSIONS: Among patients presenting with a first STEMI, there were no differences in culprit plaque features between women and men.

Impact of statins therapy on morphological changes in lipid-rich plaques stratified by 10-Year framingham risk score: A serial optical coherence tomography study.

The aim of the study was to investigate the impact of statins therapy on morphological changes of lipid-rich plaques by OCT (optical coherence tomography) in patients with known CHD (coronary heart disease), stratified by FRS. Ninety-seven lipid-rich plaques from sixty-nine patients who received statins therapy and underwent serial OCT images (baseline, 6-month and 12-month) were divided into 2 groups according to the FRS (framingham risk score): low risk group A (FRS<10%, N=35, n=45), moderate to high risk group B (FRS≥10%, N=34, n=52). Fibrous cap thickness (FCT) was measured at its thinnest part 3 times. Baseline characteristics were not different between the 2 groups. FCT sustained increased from baseline to 6-month and 12-month follow up in both group A (59.8±20.4µm, 118.3±62.5µm, and 158.8±83.4µm respectively, P<0.001) and group B (62.2±16.8µm, 125.1±78.7µm, 163.8±75.5µm respectively, P<0.001). Lipid index was significantly decreased in both group A (1862.1±1164.5, 1530.3±1108.7, 1322.9±1080.4, P<0.001) and group B (1646.6±958.5, 1535.1±1049.1, 1258.6±1045, P=0.016). The incidence of TCFA was decreased statistically in both group A (P <0.001) and group B (P <0.001). The patients with known CHD can equivalently benefit from statins therapy by stabilizing the lipid-rich plaques. Patients with moderate to high FRS might benefit more within the first year from event time.

Management and Outcome of Patients With Acute Coronary Syndrome Caused by Plaque Rupture Versus Plaque Erosion: An Intravascular Optical Coherence Tomography Study.

BACKGROUND: Plaque rupture and erosion are the 2 most common mechanisms for acute coronary syndromes. However, the outcome of these 2 distinct pathologies in patients with acute coronary syndromes has never been studied. METHODS AND RESULTS: We retrospectively studied 141 patients with acute coronary syndromes who underwent optical coherence tomography (OCT) imaging of the culprit lesion prior to stenting from the Massachusetts General Hospital OCT Registry. Management (stent versus no stent), poststent OCT findings, and outcomes were compared. Among the 141 culprit lesions, rupture was found in 79 (56%) patients and erosion in 62 (44%). Stent implantation was performed in 77 (97.5%) patients with rupture versus 49 (79.0%) in those with erosion (P<0.001). Immediately after percutaneous coronary intervention, OCT showed a higher incidence of malapposition (37.5% versus 7.3%, P<0.001), thrombus (59.4% versus 14.6%, P<0.001), and protrusion (93.8% versus 73.2%, P=0.008) in the rupture group compared with the erosion group. Plaque rupture was associated with a higher incidence of no reflow or slow flow and distal embolization. Although cardiac event rates were comparable between the two groups at the 1-year follow-up, none of the erosion patients who were treated conservatively without stenting had adverse cardiac events. CONCLUSIONS: Unfavorable poststent OCT findings were more frequent in rupture patients compared with erosion patients. A subset of erosion patients who were treated conservatively without stenting remained free of adverse cardiac events for up to 1 year.