Engineered exosomes: a potential therapeutic strategy for septic cardiomyopathy.

Septic cardiomyopathy, a life-threatening complication of sepsis, can cause acute heart failure and carry a high mortality risk. Current treatments have limitations. Fortunately, engineered exosomes, created through bioengineering technology, may represent a potential new treatment method. These exosomes can both diagnose and treat septic cardiomyopathy, playing a crucial role in its development and progression. This article examines the strategies for using engineered exosomes to protect cardiac function and treat septic cardiomyopathy. It covers three innovative aspects: exosome surface modification technology, the use of exosomes as a multifunctional drug delivery platform, and plant exosome-like nanoparticle carriers. The article highlights the ability of exosomes to deliver small molecules, proteins, and drugs, summarizing several RNA molecules, proteins, and drugs beneficial for treating septic cardiomyopathy. Although engineered exosomes are a promising biotherapeutic carrier, they face challenges in clinical application, such as understanding the interaction mechanism with host cells, distribution within the body, metabolism, and long-term safety. Further research is essential, but engineered exosomes hold promise as an effective treatment for septic cardiomyopathy.

ITIH4 reversed the effects of thrombin on VSMCs stiffness via JNK and ERK signaling pathway.

Vascular smooth muscle cell (VSMCs) is one of the important cell types in artery. VSMCs stiffening may regulate vascular stiffness and contribute to the development of vulnerable plaques. Thrombin, an enzyme in coagulation system, is involved in pathological processes of atherosclerosis. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) plays an important role in regulating inflammation and may have cardiovascular protective effect. Therefore, the elucidation of the mechanisms underlying ITIH4-mediated VSMCs stiffening helps to provide new ideas and potential targets for the diagnosis and treatment of atherosclerosis. In this study, we used specific ITIH4 expression vector and siRNA methods to transfect VSMCs. Our results found that ITIH4 expression increased VSMCs stiffness, meanwhile, ITIH4 siRNA decreased VSMCs stiffness. ITIH4 increased acetylated α-tubulin and inhibited ERK1/2 and JNK, but not P38 MAPK. JNK inhibitor (SP600125) or ERK inhibitor (PD98059) treatment increased acetylated α-tubulin expression and cell stiffness in VSMCs. ITIH4 was downregulated by thrombin treatment, ITIH4 partly reversed the effect of thrombin on acetylated α-tubulin and VSMCs stiffness. These results indicated that ITIH4 regulated acetylated α-tubulin expression in VSMCs and was against the effects of thrombin on VSMCs stiffness. JNK and ERK signaling pathways were proved to participate in this process.

Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients.

BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

Case Report of snare-assisted coaxiality optimized technique during valve deployment in patient with pure aortic regurgitation.

In high-risk patients with pure native aortic regurgitation (PNAR), transcatheter aortic valve replacement (TAVR) remains an off-label intervention. Due to anatomical variations in the aortic root and technical challenges unique to PNAR, the transfemoral approach (TF-TAVR) requires continued accumulation of experience and technological refinement. In this context, we successfully and safely performed a snare-assisted TF-TAVR procedure for a patient with PNAR, characterized by significant aortic angulation. We introduced an innovative technique termed "snare-assisted coaxiality optimized technique" (SACOT) during valve deployment. SACOT played a crucial role in optimizing valve positioning, enhancing coaxiality, and achieving the ideal implantation depth for PNAR. Post-procedure assessments demonstrated stability and the absence of paravalvular regurgitation (PVR).

Serum secreted phosphoprotein 1 level is associated with plaque vulnerability in patients with coronary artery disease.

Background: Vulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease. Methods: To reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography. Results: Macrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques. Conclusion: Elevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.

Anionic Sublattices in Halide Solid Electrolytes: A Case Study with the High-Pressure Phase of Li3ScCl6.

The Li3MX6 compounds (M=Sc, Y, In; X=Cl, Br) are known as promising ionic conductors due to their compatibility with typical metal oxide cathode materials. In this study, we have successfully synthesized γ-Li3ScCl6 using high pressure for the first time in this family. Structural analysis revealed that the high-pressure polymorph crystallizes in the polar and chiral space group P63mc with hexagonal close-packing (hcp) of anions, unlike the ambient-pressure α-Li3ScCl6 and its spinel analog with cubic closed packing (ccp) of anions. Investigation of the known Li3MX6 family further revealed that the cation/anion radius ratio, rM/rX, is the factor that determines which anion sublattice is formed and that in γ-Li3ScCl6, the difference in compressibility between Sc and Cl exceeds the ccp rM/rX threshold under pressure, enabling the ccp-to-hcp conversion. Electrochemical tests of γ-Li3ScCl6 demonstrate improved electrochemical reduction stability. These findings open up new avenues and design principles for lithium solid electrolytes, enabling routes for materials exploration and tuning electrochemical stability without compositional changes or the use of coatings.

Exploring metal(loid)s dynamics and bacterial community shifts in contaminated paddy soil: Impact of MgO-laden biochar under different water conditions.

In this study, a soil incubation experiment was conducted to explore the influence MgO-treated corn straw biochar (MCB) on the bioavailability and chemical forms of cadmium (Cd), lead (Pb), and arsenic (As), alongside the impact on the bacterial community within paddy soil subjected to both flooded and non-flooded conditions. Raw corn straw biochar (CB) served as the unmodified biochar control, aiding in the understanding of the biochar's role within the composite. The results showed that even at a minimal concentration of 0.5 %, MCB exhibited higher effectiveness in reducing the bioavailability of Pb and Cd compared to 1 % CB. In non-flooded conditions, 0.5 % MCB reduced the bioavailable Pb and Cd by 99.7 % and 87.4 %, respectively, while NaH2PO4-extracted As displayed a 14.5 % increase. With increasing MCB concentrations (from 0.5 % to 1.5 %), soil pH, DOC, EC, available phosphorus, and bioavailable As increased, while bioavailable Pb and Cd exhibited declining tendencies. Flooding did not notably alter MCB's role in reducing Pb and Cd bioavailability, yet it systematically amplified As release. Heavy metal fractions extracted by acetic acid increased in the MCB groups under flooding conditions, especially for As. The inclusion of 0.5 % MCB did not noticeably affect bacterial diversity, whereas higher doses led to reduced diversity and substantial changes in community composition. Specifically, the groups with MCB showed an increase in the Bacteroidetes and Proteobacteria phyla, accompanied by a decrease in Acidobacteria. These alterations were primarily attributed to the increased pH and EC resulting from MgO hydrolysis. Consequently, for Pb/Cd stabilization and soil bacterial diversity, a low dosage of MgO-treated biochar is recommended. However, caution is advised when employing MgO-treated biochar in soils with elevated arsenic levels, particularly under flooded conditions.

Day-night pattern of acute ST-segment elevation myocardial infarction onset in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of coronary events, especially during the nighttime. This study sought to investigate the day-night pattern of acute ST-segment elevation myocardial infarction (STEMI) onset in patients with OSA and its impact on cardiovascular adverse events. METHODS: We prospectively enrolled 397 patients with STEMI, for which the time of onset of chest pain was clearly identified. All participants were categorized into non-OSA (n = 280) and OSA (n = 117) groups. The association between STEMI onset time and major adverse cardiovascular and cerebrovascular events was estimated by Cox proportional hazards regression. RESULTS: STEMI onset occurred from midnight to 5:59 am in 33% of patients with OSA, as compared with 15% in non-OSA patients (P < .01). For individuals with OSA, the relative risk of STEMI from midnight to 5:59 am was 2.717 [95% confidence interval (CI) 1.616 - 4.568] compared with non-OSA patients. After a median of 2.89 ± 0.78 years follow-up, symptom onset time was found to be significantly associated with risk of major adverse cardiovascular and cerebrovascular events in patients with OSA, while there was no significant association observed in non-OSA patients. Compared with STEMI presenting during noon to 5:59 pm, the hazard ratios for major adverse cardiovascular and cerebrovascular events in patients with OSA were 4.683 (95% CI 2.024 - 21.409, P = .027) for midnight to 5:59 am and 6.964 (95% CI 1.379 - 35.169, P = .019) for 6 pm to midnight, whereas the hazard ratios for non-OSA patients were 1.053 (95% CI 0.394 - 2.813, P = .917) for midnight to 5:59 am and 0.745 (95% CI 0.278 - 1.995, P = .558) for 6 pm to midnight. CONCLUSIONS: Patients with OSA exhibited a peak incidence of STEMI between midnight and 5:59 am, which showed an independent association with cardiovascular adverse events. CITATION: Wang Y, Buayiximu K, Zhu T, et al. Day-night pattern of acute ST-segment elevation myocardial infarction onset in patients with obstructive sleep apnea. J Clin Sleep Med. 2024;20(5):765-775.

Key factors influencing arsenic phytotoxicity thresholds in south China acidic soils.

Arsenic (As) toxicity threshold values (TTVs) for plants are fundamental to both establishing regional As reference values in soil and performing risk assessment. However, TTVs vary with plant species and soil types. In this study, a hydroponic experiment with 16 plant species was conducted to screen the most As-sensitive plant species. The results showed that the EC20 (available As concentration at which shoot biomass or height is inhibited by 20%) values were 1.38-104.4 mg L-1 for shoot height and 0.24-42.87 mg L-1 for shoot fresh biomass. Rice was more sensitive to As toxicity than the other species. Therefore, it was chosen as the ecological receptor in the pot experiment on As phytotoxicity in nine types of soils collected from Fujian Province in South China. The EC10 and EC20 with respect to rice shoot height were 3.72-29.11 mg kg-1 and 7.12-45.60 mg kg-1, respectively. Stepwise regression analysis indicated that free iron oxide concentration is the major factor that affects As bioavailability in soil, and ECx (x = 10, 20, and 50) of soil available As for shoot height was positively related to free iron oxide concentration in soil. In addition, soil cation exchange capacity, clay (<0.002 mm) content, and exchangeable magnesium content are also important factors influencing As phytotoxicity in acidic soils. The regression models can be used to predict As phytotoxicity in acidic soils.

Predictive value of early left ventricular end-diastolic volume changes for late left ventricular remodeling after ST-elevation myocardial infarction.

BACKGROUD: Left ventricular remodeling (LVR) is a major predictor of adverse outcomes in patients with acute ST-elevation myocardial infarction (STEMI). This study aimed to prospectively evaluate LVR in patients with STEMI who were successfully treated with primary percutaneous coronary intervention (PCI) and examine the relationship between early left ventricular dilation and late LVR. METHODS: Overall 301 consecutive patients with STEMI who underwent primary PCI were included. Serial echocardiography was performed on the first day after PCI, on the day of discharge, at 1 month, and 6 months after discharge. RESULTS: Left ventricular remodeling occurred in 57 (18.9%) patients during follow-up. Left ventricular end-diastolic volume (LVEDV) reduced from day 1 postoperative to discharge in the LVR group compared with that in the non-LVR (n-LVR) group. The rates of change in LVEDV (ΔLVEDV%) were -5.24 ± 16.02% and 5.05 ± 16.92%, respectively (p < 0.001). LVEDV increased in patients with LVR compared with n-LVR at 1-month and 6-month follow-ups (ΔLVEDV% 13.05 ± 14.89% vs. -1.9 ± 12.03%; 26.46 ± 14.05% vs. -3.42 ± 10.77%, p < 0.001). Receiver operating characteristic analysis showed that early changes in LVEDV, including ΔLVEDV% at discharge and 1-month postoperative, predicted late LVR with an area under the curve value of 0.80 (95% confidence interval 0.74-0.87, p < 0.0001). CONCLUSIONS: Decreased LVEDV at discharge and increased LVEDV at 1-month follow-up were both associated with late LVR at 6-month. Comprehensive and early monitoring of LVEDV changes may help to predict LVR.

Enhanced tyrosine sulfation is associated with chronic kidney disease-related atherosclerosis.

BACKGROUND: Chronic kidney disease (CKD) accelerates atherosclerosis, but the mechanisms remain unclear. Tyrosine sulfation has been recognized as a key post-translational modification (PTM) in regulation of various cellular processes, and the sulfated adhesion molecules and chemokine receptors have been shown to participate in the pathogenesis of atherosclerosis via enhancement of monocyte/macrophage function. The levels of inorganic sulfate, the essential substrate for the sulfation reaction, are dramatically increased in patients with CKD, which indicates a change of sulfation status in CKD patients. Thus, in the present study, we detected the sulfation status in CKD patients and probed into the impact of sulfation on CKD-related atherosclerosis by targeting tyrosine sulfation function. RESULTS: PBMCs from individuals with CKD showed higher amounts of total sulfotyrosine and tyrosylprotein sulfotransferase (TPST) type 1 and 2 protein levels. The plasma level of O-sulfotyrosine, the metabolic end product of tyrosine sulfation, increased significantly in CKD patients. Statistically, O-sulfotyrosine and the coronary atherosclerosis severity SYNTAX score positively correlated. Mechanically, more sulfate-positive nucleated cells in peripheral blood and more abundant infiltration of sulfated macrophages in deteriorated vascular plaques in CKD ApoE null mice were noted. Knockout of TPST1 and TPST2 decreased atherosclerosis and peritoneal macrophage adherence and migration in CKD condition. The sulfation of the chemokine receptors, CCR2 and CCR5, was increased in PBMCs from CKD patients. CONCLUSIONS: CKD is associated with increased sulfation status. Increased sulfation contributes to monocyte/macrophage activation and might be involved in CKD-related atherosclerosis. Inhibition of sulfation may suppress CKD-related atherosclerosis and is worthy of further study.

Brachial and central hypertension in relation to coronary stenosis in patients with coronary angiography.

The clinical significance of central beyond brachial blood pressure (BP) remains unclear. In patients who underwent coronary angiography, the authors explored whether elevated central BP would be associated with coronary arterial disease (CAD) irrespective of the status of brachial hypertension. From March 2021 to April 2022, 335 patients (mean age 64.9 years, 69.9% men) hospitalized for suspected CAD or unstable angina were screened in an ongoing trial. CAD was defined if a coronary stenosis of ≥50%. According to the presence of brachial (non-invasive cuff systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) and central (invasive systolic BP ≥130 mmHg) hypertension, patients were cross-classified as isolated brachial hypertension (n = 23), isolated central hypertension (n = 93), and concordant normotension (n = 100) or hypertension (n = 119). In continuous analyses, both brachial and central systolic BPs were significantly related to CAD with similar standardized odds ratios (OR, 1.47 and 1.45, p < .05). While categorical analyses showed that patients with isolated central hypertension or concordant hypertension had a significantly higher prevalence of CAD and the Gensini score than those with concordant normotension. Multivariate-adjusted OR (95% confidence interval [CI]) for CAD was 2.24 (1.16 to 4.33, p = .009) for isolated central hypertension and 3.02 (1.58 to 5.78, p < .001) for concordant hypertension relative to concordant normotension. The corresponding OR (95% CI) of a high Gensini score was 2.40 (1.26-4.58) and 2.17 (1.19-3.96), respectively. In conclusion, regardless of the presence of brachial hypertension, elevated central BP was associated with the presence and severity of CAD, indicating that central hypertension is an important risk factor for coronary atherosclerosis.

Effects of low-dose furosemide combined with aminophylline on the renal function in septic shock patients.

BACKGROUND: To investigate the effects of low-dose furosemide and aminophylline on the renal function in patients with septic shock. METHODS AND RESULTS: A total of 109 eligible septic shock patients in the intensive care unit were randomly divided into a control group (n = 55) and an intervention group (n = 54). The control group received normal saline, and the intervention group received low-dose furosemide (0.048 mg/kg.h-1) with aminophylline (0.3 mg/kg.h-1). The primary outcomes included the levels of serum creatinine (Scr), creatinine clearance rate (Ccr), blood urea nitrogen (BUN), glomerular filtration rate (GFR), and urine output on admission and on days 3, 7 and 14. The secondary outcomes were the sequential organ failure assessment (SOFA) scores, continuous renal replacement therapy (CRRT) time and intensive care unit (ICU) mortality, hospital mortality and 28-day mortality. There were no significant differences in the levels of Scr, Ccr, BUN, or GFR between the two groups, while the urine output was higher in the intervention group on days 3, 7, and 14. Compared with the control group, the SOFA scores, ICU mortality, hospital mortality and 28-day mortality were significantly lower in the intervention group on days 3, 7, and 14, the CRRT time was shorter, and the cumulative fluid balance was lower on days 3 and 7 in the intervention group. CONCLUSIONS: Although low-dose furosemide and aminophylline have fewer protective effects on the renal function in septic shock patients, they could reduce the CRRT time and improve the prognosis.

NaRb6(B4O5(OH)4)3(BO2) Featuring Noncentrosymmetry, Chirality, and the Linear Anionic Group BO2.

Noncentrosymmetric (NCS) structures are of particular interest owing to their symmetry-dependent physical properties, e.g., pyroelectricity, ferroelectricity, piezoelectricity, and nonlinear optical (NLO) behavior. Among them, chiral materials exhibit polarization rotation and host topological properties. Borates often contribute to NCS and chiral structures via their triangular [BO3] and tetrahedral [BO4] units and their numerous superstructure motifs. However, no chiral compound with the linear [BO2] unit has been reported to date. Herein, an NCS and chiral mixed-alkali-metal borate, NaRb6(B4O5(OH)4)3(BO2), with a linear BO2- unit in the structure was synthesized and characterized. The structure features a combination of three types of basic building units (BBUs), [BO2], [BO3], and [BO4] with sp-, sp2-, and sp3-hybridization of boron atoms, respectively. It crystallizes in the trigonal space group R32 (No. 155), one of the 65 Sohncke space groups. Two enantiomers of NaRb6(B4O5(OH)4)3(BO2) were found, and their crystallographic relationships are discussed. These results not only expand the small family of NCS structures with the rare linear BO2- unit but also prompt recognition to the fact that NLO materials have generally overlooked the existence of two enantiomers in achiral Sohncke space groups.

Association of Serum BAFF Levels with Cardiovascular Events in ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The B cell activating factor (BAFF) is a B cell survival factor involved in atherosclerosis and ischemia-reperfusion (IR) injury. This study sought to investigate whether BAFF is a potential predictor of poor outcomes in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We prospectively enrolled 299 patients with STEMI, and serum levels of BAFF were measured. All subjects were followed for three years. The primary endpoint was major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal reinfarction, hospitalization for heart failure (HF), and stroke. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of BAFF for MACEs. RESULTS: In multivariate analysis, BAFF was independently associated with risk of MACEs (adjusted HR 1.525, 95% CI 1.085-2.145; p = 0.015) and cardiovascular death (adjusted hazard ratio [HR] 3.632, 95% confidence interval [CI] 1.132-11.650, p = 0.030) after adjustment for traditional risk factors. Kaplan-Meier survival curves demonstrated that patients with BAFF levels above the cut-off value (1.46 ng/mL) were more likely to have MACEs (log-rank p < 0.0001) and cardiovascular death (log-rank p < 0.0001). In subgroup analysis, the impact of high BAFF on MACEs development was stronger in patients without dyslipidemia. Furthermore, the C-statistic and Integrated Discrimination Improvement (IDI) values for MACEs were improved with BAFF as an independent risk factor or when combined with cardiac troponin I. CONCLUSIONS: This study suggests that higher BAFF levels in the acute phase are an independent predictor of the incidence of MACEs in patients with STEMI.

Prognostic value of post-procedural µQFR for drug-coated balloons in the treatment of in-stent restenosis.

BACKGROUND: Investigating the prognostic value of the Murray law-based quantitative flow ratio (µQFR) on the clinical outcome after treatment of in-stent restenosis (ISR) with a drug-coated balloon (DCB). METHODS: Patients participating in a previous randomized clinical trial for DCB-ISR were post-hoc analyzed. The primary endpoint was vessel-oriented composite endpoint (VOCE), defined as cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. µQFRs at baseline and after DCB angioplasty was calculated, and its prognostic value as a predictor of VOCE was explored in Cox regression. RESULTS: A total of 169 lesions in 169 patients were analyzed. At 1-year follow-up, 20 VOCEs occurred in 20 patients. Receiver-operating characteristic curve analysis identified a post-procedural µQFR of ≤ 0.89 as the best cut-off to predict VOCE (area under curve [AUC]: 0.74; 95% confidence interval [CI]: 0.67-0.80; p < 0.001), superior to post-procedural in-stent percent diameter stenosis, which reported an AUC of 0.61 (95% CI: 0.53-0.68; p = 0.18). Post-procedural µQFR was significantly lower in patients with VOCE compared with those without (0.88 [interquartile range: 0.79-0.94] vs. 0.96 [interquartile range: 0.91-0.98], respectively; p < 0.001). After correction for potential confounders, post-procedural µQFR ≤ 0.89 was associated with a 6-fold higher risk of VOCE than lesions with µQFR > 0.89 (hazard ratio: 5.94; 95% CI: 2.33-15.09; p < 0.001). CONCLUSIONS: Post-procedural µQFR may become a promising predictor of clinical outcome after treatment of DES-ISR lesions by DCB angioplasty.

Automatic assessment of collaterals physiology in chronic total occlusions by means of artificial intelligence.

BACKGROUND: Assessment of collaterals physiology in chronic total occlusions (CTO) currently requires dedicated devices, adds complexity, and increases the cost of the intervention. This study sought to derive collaterals physiology from flow velocity changes (ΔV) in donor arteries, calculated with artificial intelligence- aided angiography. METHODS: Angiographies with successful percutaneous coronary intervention (PCI) in 2 centers were retro- spectively analyzed. CTO collaterals were angiographically evaluated according to Rentrop and collateral connections (CC) classifications. Flow velocities in the primary and secondary collateral donor arteries (PCDA, SCDA) were automatically computed pre and post PCI, based on a novel deep-learning model to extract the length/time curve of the coronary filling in angiography. Parameters of collaterals physiology, Δcollateral-flow (Δfcoll) and Δcollateral-flow-index (ΔCFI), were derived from the ΔV pre-post. RESULTS: The analysis was feasible in 105 out of 130 patients. Flow velocity in the PCDA significantly decreased after CTO-PCI, proportionally to the angiographic collateral grading (Rentrop 1: 0.02 ± 0.01 m/s; Rentrop 2: 0.04 ± 0.01 m/s; Rentrop 3: 0.07 ± 0.02 m/s; p < 0.001; CC0: 0.01 ± 0.01 m/s; CC1: 0.04 ± ± 0.02 m/s; CC2: 0.06 ± 0.02 m/s; p < 0.001). Δfcoll and ΔCFI paralleled ΔV. SCDA also showed a greater reduction in flow velocity if its collateral channels were CC1 vs. CC0 (0.03 ± 0.01 vs. 0.01 ± 0.01 m/s; p < 0.001). For each individual patient, ΔV was more pronounced in the PCDA than in the SCDA. CONCLUSIONS: Automatic assessment of collaterals physiology in CTO is feasible, based on a deeplearning model analyzing the filling of the donor vessels in angiography. The changes in collateral flow with this novel method are quantitatively proportional to the angiographic grading of the collaterals.

SerpinG1: A Novel Biomarker Associated With Poor Coronary Collateral in Patients With Stable Coronary Disease and Chronic Total Occlusion.

Background This study aimed to explore predictive biomarkers of coronary collateralization in patients with chronic total occlusion. Methods and Results By using a microarray expression profiling program downloaded from the Gene Expression Omnibus database, weighted gene coexpression network analysis was constructed to analyze the relationship between potential modules and coronary collateralization and screen out the hub genes. Then, the hub gene was identified and validated in an independent cohort of patients (including 299 patients with good arteriogenic responders and 223 patients with poor arteriogenic responders). Weighted gene coexpression network analysis showed that SERPING1 in the light-cyan module was the only gene that was highly correlated with both the gene module and the clinical traits. Serum levels of serpinG1 were significantly higher in patients with bad arteriogenic responders than in patients with good arteriogenic responders (472.53±197.16 versus 314.80±208.92 µg/mL; P<0.001) and were negatively associated with the Rentrop score (Spearman r=-0.50; P<0.001). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.77 (95% CI, 0.72-0.81; P<0.001) for serum serpinG1 in prediction of bad arteriogenic responders. After adjusting for traditional cardiovascular risk factors, serum serpinG1 levels (per SD) remained an independent risk factor for bad arteriogenic responders (odds ratio, 2.20 [95% CI, 1.76-2.74]; P<0.001). Conclusions Our findings illustrate that SERPING1 screened by weighted gene coexpression network analysis was associated with poor collateralization in patients with chronic total occlusion.

Serum MPO levels and activities are associated with angiographic coronary atherosclerotic plaque progression in type 2 diabetic patients.

BACKGROUND: The uncontrolled production of MPO promotes inflammation, oxidative stress and atherosclerosis. Serum MPO levels are increased in patients with diabetes compared with patients without diabetes. OBJECTIVES: This study aimed to investigate whether the serum levels and activities of MPO are related to coronary plaque progression in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: Serum MPO levels and activities were measured in 161 patients with diabetes with plaque progression (plaque progression group) and 87 patients with diabetes with no plaque progression (no plaque progression group). These patients were eligible based on the inclusion criteria and received quantitative coronary angiography at baseline and after approximately 1 year of follow-up. The characteristics and parameters of the participants at baseline were documented. RESULTS: Serum MPO levels and activities were significantly higher in plaque progression group than in no plaque progression group (P < 0.001). We categorized these patients with diabetes into MPO level or activity tertile subgroups. Significant differences in the plaque progression ratio and prominent changes in the minimal lumen diameter, stenosis diameter and coronary artery stenosis score were observed across the tertile subgroups of MPO levels and activities (all P < 0.01). Moreover, serum MPO levels and activities correlated significantly with these indices of coronary artery disease severity after adjustment for other risk factors. Multivariable regression analyses revealed that serum MPO levels and activities remained independently associated with plaque progression, in addition to smoking, hypertension and CRP levels (all P < 0.05). CONCLUSIONS: Serum MPO levels and activities are significantly associated with coronary atherosclerotic plaque progression in patients with type 2 diabetes.

Serum apolipoprotein A-IV levels are associated with flow-mediated dilation in patients with type 2 diabetes mellitus.

BACKGROUND: Endothelial dysfunction is common in diabetes. Apolipoprotein (apo) A-IV functions to antagonize inflammation and oxidative stress. The present study aimed to investigate the relationship between flow-mediated dilation (FMD) and serum apoA-IV level in type 2 diabetes mellitus (T2DM) patients.  METHODS: A total of 84 T2DM patients with chest discomfort were enrolled in this study. Their baseline characteristics and clinical parameters were documented. Endothelial function of the participants was evaluated by examining FMD of brachial artery. The severity of coronary atherosclerosis was determined by quantitative coronary angiography. Serum apoA-IV levels were measured by ELISA. RESULTS: These diabetic patients were dichotomized into low FMD (n = 42) and high FMD (n = 42) groups. Serum apoA-IV levels were significantly higher in high FMD group than in low FMD group (29.96 ± 13.17 vs 17.69 ± 9.16 mg/dL, P < 0.001). Moreover, the patients were also categorized into three apoA-IV tertile groups. FMD was significantly different across three apoA-IV tertiles (P < 0.001). Serum apoA-IV levels were positively correlated to FMD (r = 0.469, P < 0.001). Logistic regression analysis was performed to determine risk factors for low FMD. apoA-IV levels together with the risk factor hsCRP remained significantly to be independent determinants of low FMD (P < 0.01). Linear regression analysis was performed, and apoA-IV levels together with total-to-HDL cholesterol ratio were independently correlated with FMD (P < 0.01). CONCLUSIONS: Serum apoA-IV levels are associated with FMD, suggesting that apoA-IV protects endothelial function in patients with T2DM.