A single site ruthenium catalyst for robust soot oxidation without platinum or palladium.

The quest for efficient non-Pt/Pd catalysts has proved to be a formidable challenge for auto-exhaust purification. Herein, we present an approach to construct a robust catalyst by embedding single-atom Ru sites onto the surface of CeO2 through a gas bubbling-assisted membrane deposition method. The formed single-atom Ru sites, which occupy surface lattice sites of CeO2, can improve activation efficiency for NO and O2. Remarkably, the Ru1/CeO2 catalyst exhibits exceptional catalytic performance and stability during auto-exhaust carbon particle oxidation (soot), rivaling commercial Pt-based catalysts. The turnover frequency (0.218 h-1) is a nine-fold increase relative to the Ru nanoparticle catalyst. We further show that the strong interfacial charge transfer within the atomically dispersed Ru active site greatly enhances the rate-determining step of NO oxidation, resulting in a substantial reduction of the apparent activation energy during soot oxidation. The single-atom Ru catalyst represents a step toward reducing dependence on Pt/Pd-based catalysts.

Plasma levels of bone morphogenic protein-4 are downregulated in elderly hypertensive patients with heart failure with preserved ejection fraction.

OBJECTIVE: This study aimed to evaluate the association between plasma bone morphogenic protein-4 (BMP-4) levels and heart failure (HF) with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF) in elderly hypertensive patients. METHODS: A total of 222 hypertensive individuals meeting the inclusion criteria were enrolled from October 2021 to July 2022. Data were collected including clinical characteristics, laboratory tests and echocardiogram measurements. Plasma BMP-4 levels were tested using enzyme-linked immunosorbent assay analysis. RESULTS: Among 222 elderly hypertensive patients, 149 were without HF, 59 had HFpEF, and 14 had HFmrEF. Plasma BMP-4 levels were strikingly downregulated in hypertensive patients with HFpEF/HFmrEF [median (25th, 75th percentile): 15.89 (7.69, 23.12) pg/mL vs. 19.67 (10.60, 33.04) pg/mL; P = 0.002]. After univariate and multivariate logistic regression analysis, the risk of HFpEF/HFmrEF was declined in the 4th quartile BMP-4 group when compared with the 1st quartile BMP-4 group (odds ratio, 0.20, 95% confidence interval (CI), 0.04 to 1.00; P = 0.050, P for trend = 0.025). Receiver operating characteristic curve analysis revealed that BMP-4 ≤ 28.5 pg/mL exhibited a sensitivity of 95.9% and a specificity of 28.2% in HFpEF/HFmrEF diagnosis. Furthermore, the area under the curve (AUC) was 0.619 (95% CI:0.540-0.698, P < 0.001). The corresponding AUC for brain natriuretic peptide (BNP) was 0.781 (95% CI: 0.710-0.852), P < 0.001. Adding BMP-4 to BNP increased the AUC to 0.790 (95% CI: 0.724-0.856), vs. BMP-4, P < 0.001; vs. BNP, P = 0.730, respectively. CONCLUSIONS: Plasma BMP-4 levels are downregulated in elderly hypertensive patients with HFpEF. BMP-4 is a promising biomarker for diagnosing HFpEF/HFmrEF during hypertension.

Circulating exosomal lncRNAs in patients with chronic coronary syndromes.

Introduction: The concept of chronic coronary syndrome (CCS) was first presented at the European Society of Cardiology Meeting in 2019. However, the roles of exosomal lncRNAs in CCS remain largely unclear. Material and methods: A case-control study was performed with a total of 218 participants (137 males and 81 females), including 15 CCS patients and 15 controls for sequencing profiles, 20 CCS patients and 20 controls for the first validation, and 100 CCS patients and 48 controls for the second validation. Exosomes were isolated from the plasma of CCS patients and controls, and exosomal lncRNAs were identified by sequencing profiles and verified twice by qRT-PCR analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exosomal lncRNAs for CCS patients. Results: A total of 152 significantly differentially expressed lncRNAs with over two-fold changes were detected in plasma exosomes of CCS patients, including 90 upregulated and 62 downregulated lncRNAs. Importantly, 6 upregulated lncRNAs with the top fold changes were selected for validations. Exosomal lncRNAs ENST00000424615.2 and ENST00000560769.1 were significantly elevated in CCS patients in both validations compared with controls. The areas under the ROC of lncRNAs ENST00000424615.2 and ENST00000560769.1 were 0.654 and 0.722, respectively. Additionally, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels (p = 0.028). Conclusions: Exosomal lncRNA ENST00000424615.2 and ENST00000560769.1 were identified as novel diagnosis biomarkers for patients with CCS. Moreover, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels, and might be associated with a poor prognosis.

Effects of intensive blood pressure lowering in patients with diabetes: A pooled analysis of the STEP and ACCORD-BP randomized trials.

AIM: To determine whether intensive systolic blood pressure (SBP) lowering can benefit hypertensive patients with diabetes. MATERIALS AND METHODS: We performed a pooled analysis of individual patient data from two randomized trials to compare intensive and standard SBP targets in hypertensive patients with diabetes (STEP diabetes subgroup and ACCORD-BP standard glycaemic group, n = 1627 and n = 2362, respectively). We defined a modified primary outcome as a composite of stroke, major coronary artery disease (myocardial infarction and unstable angina), heart failure, and cardiovascular death. The secondary outcomes were individual components of the primary outcome and death from any cause. A Cox proportional hazards regression model was used in the main analysis. We conducted one-stage mixed-effect models and two-stage analyses as sensitivity and supplementary analyses to verify the robustness of the findings. RESULTS: A total of 3989 patients were randomized to undergo intensive (n = 1984) or standard SBP treatment (n = 2005). After a median follow-up of 3.83 years, the primary outcome occurred in 193/1984 patients in the intensive group and in 247/2005 patients in the standard group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.64-0.93). The incidence rates for secondary outcomes were lower in the intensive group than in the standard group, but were not significantly different, except for stroke (intensive vs. standard: 32/1984 vs. 58/2005; HR 0.56, 95% CI 0.36-0.86). These results remained consistent in the additional sensitivity and supplementary analyses. CONCLUSIONS: An intensive SBP-lowering target of 110 to <130 mmHg reduces the cardiovascular outcomes compared with a standard SBP-lowering target of 130 to <150 mmHg. The findings of this study support the favourable effects of intensive SBP lowering in hypertensive patients with diabetes.

Association of the visceral adiposity index with arterial stiffness in elderly Chinese population.

BACKGROUND: The visceral adiposity index (VAI) is a new marker of adipose dysfunction and related with cardiometabolic risk. The aim of this study is to investigate the association of VAI with arterial stiffness in elderly Chinese population. METHODS: A total of 1,707 elderly individuals over 60 years of age were recruited for this cross-sectional study. We measured body composition, anthropometrics, blood pressure, and lipid parameters. The arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) and defined as baPWV ≥ 1400 cm/s. VAI‬ was calculated based on body mass index, waist circumference, triglyceride and high-density lipoprotein cholesterol. Multivariable regression analysis was performed to evaluate the association between VAI and baPWV. RESULTS: There were significant differences in VAI tertiles between low-baPWV and high-baPWV group (p = 0.008). Univariate analysis demonstrated that age, history of hypertension, SBP, DBP, total cholesterol, fasting glucose, the higher VAI tertiles were correlated with the existence of high-baPWV (p < 0.05). Participants in the higher VAI tertiles had higher OR (1.0 ≤ VAI < 1.74: OR= 2.89, 95% CI [1.44, 5.80]; VAI ≥ 1.75: OR = 4.23, 95% CI [1.45, 12.37], p for trend: 0.004) comparing with the lowest VAI tertile. Non-linear relationship was detected between VAI and baPWV. VAI was positively correlated with baPWV when VAI < 2.10. CONCLUSIONS: This study demonstrates that VAI is independently associated with the risk of arterial stiffness in elderly population.

The association between visceral adiposity index and leukocyte telomere length in adults: results from National Health and Nutrition Examination Survey.

BACKGROUND: Leukocyte telomere length (LTL) is a robust marker of biological aging, which is associated with obesity. Recently, the visceral adiposity index (VAI) has been proposed as an indicator of adipose distribution and function. OBJECTIVE: To evaluated the association between VAI and LTL in adult Americans. METHODS: There were 3193 participants in U.S. National Health and Nutrition Examination Surveys (1999-2002) included in this analysis. LTL was measured using quantitative PCR (qPCR) and expressed as telomere to single-gene copy ratio (T/S ratio). We performed multiple logistic regression models to explore the association between VAI and LTL by adjusting for potential confounders. RESULTS: Among all participants, VAI was associated with the shorter LTL (ß: - 14.81, 95% CI - 22.28 to - 7.34, p < 0.001). There were significant differences of LTL in VAI tertiles (p < 0.001). Participants in the higher VAI tertile had the shorter LTL (1.26 ≤ VAI < 2.46: ß = - 130.16, 95% CI [ - 183.44, - 76.87]; VAI ≥ 2.46: ß = - 216.12, 95% CI [ - 216.12, - 81.42], p for trend: < 0.001) comparing with the lower VAI tertile. We also found a non-linear relationship between VAI and LTL. VAI was negatively correlated with LTL when VAI was less than 2.84. CONCLUSIONS: The present study demonstrates that VAI is independently associated with telomere length. A higher VAI is associated with shorter LTL. The results suggest that VAI may provide prediction for LTL and account for accelerating the biological aging.

Predictive value of CTRP3 for the disease recurrence of atrial fibrillation patients after radiofrequency ablation.

OBJECTIVE: To explore the expression of plasma CTRP3 in patients with non-valvular paroxysmal atrial fibrillation after radiofrequency ablation and its predictive value for disease recurrence. METHODS: In this retrospective study, the patients in the Heart Center of Beijing Chaoyang Hospital from June 2016 to November 2017 were collected. According to the guidelines for diagnosis and treatment of atrial fibrillation 2016, patients diagnosed with paroxysmal atrial fibrillation were selected as the study subjects. All patients with successful radiofrequency ablation of atrial fibrillation were followed up by telephone or outpatient service at 1, 3, 6 and 12 months after radiofrequency ablation, respectively. Recurrence of atrial fibrillation was defined as a duration of rapid atrial arrhythmia ≥30 seconds confirmed by electrocardiogram or 24-hour ambulatory electrocardiogram 3 months after radiofrequency ablation. According to the follow-up results, the patients were divided into a recurrent group and non-recurrent group. The level of CTRP3 was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Analysis of clinical baseline data showed significant differences between the recurrent group and the non-recurrent group in age, systolic blood pressure, diastolic blood pressure, EGFR, thyroid stimulating hormone level, platelet count, high-sensitivity C-reactive protein, NT proBNP, left atrial anterior posterior diameter, left atrial upper and lower diameter and CTRP3 (P < 0.05). The univariate logistic regression showed that older age (or = 1.08, P < 0.001), increased diastolic blood pressure (OR = 1.051, P = 0.002), cardiac dysfunction (OR = 2.594, P = 0.01), high-sensitivity C-reactive protein (OR = 1.134, P = 0.008) and NT proBNP (OR = 1.000, P = 0.005), increased anterior posterior diameter of left atrium (OR = 1.158, P < 0.001), increased upper and lower diameter of left atrium (OR = 1.133, P < 0.001), thrombocytopenia (OR = -0.008, P < 0.027) and CTRP3 (OR = 1.007, P = 0.006) were the risk factors for the recurrence of atrial fibrillation after radiofrequency ablation. Moreover, the multivariate logistic regression analysis demonstrated that CTRP3 (or = 1.032, P = 0.005) was an independent predictor of recurrence. CONCLUSION: The plasma concentration of CTRP3 increased significantly in patients with recurrent atrial fibrillation after radiofrequency ablation. Moreover, CTRP3 was a predictor of recurrence after radiofrequency ablation in patients with atrial fibrillation.

Facilitating Catalytic Purification of Auto-Exhaust Carbon Particles via the Fe2O3{113} Facet-dependent Effect in Pt/Fe2O3 Catalysts.

The purification efficiency of auto-exhaust carbon particles in the catalytic aftertreatment system of vehicle exhaust is strongly dependent on the interface nanostructure between the noble metal component and oxide supports. Herein, we have elaborately synthesized the catalysts (Pt/Fe2O3-R) of Pt nanoparticles decorated on the hexagonal bipyramid α-Fe2O3 nanocrystals with co-exposed twelve {113} and six {104} facets. The area ratios (R) of co-exposed {113} to {104} facets in α-Fe2O3 nanocrystals were adjusted by the fluoride ion concentration in the hydrothermal method. The strong Pt-Fe2O3{113} facet interaction boosts the formation of coordination unsaturated ferric sites for enhancing adsorption/activation of O2 and NO. Pt/Fe2O3-R catalysts exhibited the Fe2O3{113} facet-dependent performance during catalytic purification of soot particles in the presence of H2O. Among the catalysts, the Pt/Fe2O3-19 catalyst exhibits the highest catalytic activities (T50 = 365 °C, TOF = 0.13 h-1), the lowest apparent activation energy (69 kJ mol-1), and excellent catalytic stability during soot purification. Combined with the results of characterizations and density functional theory calculations, the catalytic mechanism is proposed: the active sites located at the Pt-Fe2O3{113} interface can boost the key step of NO oxidation to NO2. The crystal facet engineering is an effective strategy to obtain efficient catalysts for soot purification in practical applications.

Genetic deletion of CMG2 exacerbates systemic-to-pulmonary shunt-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD-PAH) with systemic-to-pulmonary shunt (SPS) is characterized by proliferative vascular remodeling. Capillary morphogenesis gene-2 (CMG2) plays a key role in cell proliferation and apoptosis. This study aimed to determine the role of CMG2 in the pathogenesis of SPS-induced PAH. CMG2 levels were significantly downregulated in pulmonary arterioles from patients with Eisenmenger syndrome and rats with SPS-induced PAH. CMG2 was highly expressed in several cells including human pulmonary arterial smooth muscle cells (HPASMCs). CMG2-/- rats exhibited more severe PAH and pulmonary vascular remodeling than wild-type rats when exposed to SPS for 8 weeks. Overexpression of CMG2 significantly inhibited proliferation and promoted apoptosis of HPASMCs, while knockdown of CMG2 promoted cell proliferation and inhibited cell apoptosis. Next-generation sequencing and subsequent validation results suggested that PI3K-AKT was the most prominent signaling pathway regulated by differentially expressed genes (DEGs) in CMG2-/- rat lungs. Our work identified a novel role for CMG2 in SPS-induced PAH based on the findings that CMG2 deficiency exacerbates SPS-induced vascular remodeling in the development of PAH, indicating that CMG2 might act as a potential target for the treatment of CHD-PAH.

p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced by L3MBTL4 in Essential Hypertension.

AIM: Hypertension is a complicated disorder with multifactorial etiology and high heritability. Our previous work has identified L3MBTL4 as a novel susceptibility gene for the development of essential hypertension, accompanied with activation of p38/JNK. Yet, little evidence has been reported whether p38/JNK contributed directly to L3MBTL4-induced vascular remodeling and exploring the potential mechanism of L3MBTL4 in vascular smooth muscle cells (VSMCs). METHODS: We evaluated the contribution of L3MBTL4 on proliferation, migration, and phenotype changes of VSMCs and further explored the critical role of p38 and JNK signaling pathway underlying. RESULTS: In L3MBTL4 transgenic rats, we found that the elevated blood pressure, increased left ventricular hypertrophy, and thickened vascular media layer were significantly relieved by both p38 and JNK inhibitors. Meanwhile, increased cell proliferation, advanced cell cycle progression, greater migratory capability, and synthetic phenotype were observed in L3MBTL4 overexpressed VSMCs, which could be blocked by either p38 or JNK inhibitor. CONCLUSIONS: Our findings pinpointed that p38 and JNK were required for the proliferation and phenotype changes of VSMCs induced by L3MBTL4 in hypertension. These novel findings yield new insights into the genetic and biological basis of hypertension and are fundamental for further studies to explore the intervention strategies targeting L3MBTL4 and p38/JNK to counteract the progression of hypertension.

Vital Roles of Gremlin-1 in Pulmonary Arterial Hypertension Induced by Systemic-to-Pulmonary Shunts.

Background Heterozygous mutation in BMP (bone morphogenetic protein) receptor 2 is rare, but BMP cascade suppression is common in congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH); however, the underling mechanism of BMP cascade suppression independent of BMP receptor 2 mutation is unknown. Methods and Results Pulmonary hypertensive status observed in CHD-PAH was surgically reproduced in rats. Gremlin-1 expression was increased, but BMP cascade was suppressed, in lungs from CHD-PAH patients and shunted rats, whereas shunt correction retarded these trends in rats. Immunostaining demonstrated increased gremlin-1 was mainly in the endothelium and media of remodeled pulmonary arteries. However, mechanical stretch time- and amplitude-dependently stimulated gremlin-1 secretion and suppressed BMP cascade in distal pulmonary arterial smooth muscle cells from healthy rats. Under static condition, gremlin-1 significantly promoted the proliferation and inhibited the apoptosis of distal pulmonary arterial smooth muscle cells from healthy rats via BMP cascade. Furthermore, plasma gremlin-1 closely correlated with hemodynamic parameters in CHD-PAH patients and shunted rats. Conclusions Serving as an endogenous antagonist of BMP cascade, the increase of gremlin-1 in CHD-PAH may present a reasonable mechanism explanation for BMP cascade suppression independent of BMP receptor 2 mutation.

MicroRNA-122 aggravates angiotensin II-mediated apoptosis and autophagy imbalance in rat aortic adventitial fibroblasts via the modulation of SIRT6-elabela-ACE2 signaling.

Abnormal aortic adventitial fibroblasts (AFs) play essential roles in the development of vascular remodeling and disorders. Previous studies revealed that microRNA-122 (miR-122) levels were elevated in the aortic adventitia of hypertensive rats with vascular injury. Here, we aim to evaluate the biological effects and underlying mechanisms of miR-122 in rat AFs. Exposure to angiotensin II (ATII) in rat AFs resulted in decreased levels of sirtuin 6 (SIRT6), elabela (ELA), and angiotensin-converting enzyme 2 (ACE2). Additionally, stimulation with ATII contributed to a decline in autophagic flux and obvious increases in cellular migration, oxidative stress, and apoptosis, which were exacerbated by the transfection of miR-122-5p mimic but were rescued by miR-122-5p inhibitor, exogenous replenishment of ELA, and recombinant adeno-associated virus expressing SIRT6 (rAAV-SIRT6), respectively. Moreover, stimulation with miR-122-5p mimic led to a marked reduction in the levels of SIRT6 and ELA in rat AFs, which were elevated by stimulation with rAAV-SIRT6. Furthermore, miR-122-5p inhibitor-mediated pro-autophagic, anti-oxidant and anti-apoptotic effects in rat AFs were partially suppressed by 3-methyladenine, SIRT6 small interfering RNA (siRNA) and ELA siRNA, which were linked with the downregulation in the protein levels of LC3-II, beclin-1, and ACE2 and the upregulation of p62 expression and bax/bcl-2 ratio. Our findings indicated that miR-122-5p inhibition prevented ATII-mediated loss of autophagy, and the promotion of apoptosis and oxidative stress via activating the SIRT6-ELA-ACE2 signaling. MiR-122-5p may be a novel predictive biomarker of adventitial injury, and targeting the SIRT6-ELA-ACE2 signaling may have the potential therapeutic importance of controlling vascular remodeling and disorders.

Circulating Connective Tissue Growth Factor Is Associated with Diastolic Dysfunction in Patients with Diastolic Heart Failure.

BACKGROUND: Connective tissue growth factor (CTGF) and transforming growth factor ß1 (TGF-ß1) are emerging biomarkers for tissue fibrosis. The aim of this study was to investigate the association between circulating CTGF, TGF-ß1 levels and cardiac diastolic dysfunction in patients with diastolic heart failure (DHF). METHODS: Admitted subjects were screened for heart failure and those with left ventricular (LV) ejection fraction <45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Totally 114 patients with DHF and 72 controls were enrolled. Plasma levels of CTGF, TGF-ß1, and B-type natriuretic peptide (BNP) were determined. RESULTS: The plasma CTGF and TGF-ß1 levels increased significantly in patients with DHF. Circulating CTGF and TGF-ß1 levels were correlated with echocardiographic parameter E/e' and diastolic dysfunction grading in DHF patients. In multivariate logistic analysis, CTGF was significantly associated with diastolic dysfunction (odds ratio: 1.027, p < 0.001). Plasma CTGF (AUC: 0.770 ± 0.036, p < 0.001) and CTGF/BNP (AUC: 0.839 ± 0.036, p < 0.001) showed good predictive power to the diagnosis of DHF. CONCLUSIONS: This finding suggested CTGF could be involved in the pathophysiology of diastolic heart failure and CTGF/BNP might have auxiliary diagnostic value on diastolic heart failure.

The association between orthostatic blood pressure changes and subclinical target organ damage in subjects over 60 years old.

BACKGROUND: Although recent studies have indicated that both orthostatic hypotension and orthostatic hypertension independently predict cardiovascular events, the underlying mechanisms are still controversial. The aim of the study was to investigate the relationships between orthostatic changes and organ damage in subjects over 60 years old. METHODS: This is a prospective observational cohort study. One thousand nine hundred and ninety-seven subjects over 60 years old were enrolled. Participants were grouped according to whether they had a drop ≥ 20 mmHg in systolic or ≥ 10 mmHg in diastolic BP (orthostatic hypotension), an increase in mean orthostatic systolic blood pressure ≥ 20 mm Hg (orthostatic hypertension), or normal changes within 3 min of orthostatism. Multiple regression modeling was used to investigate the relationship between orthostatic hypotension, orthostatic hypertension and subclinical organ damage with adjustment for confounders. RESULTS: Orthostatic hypotension and orthostatic hypertension were found in 461 (23.1%) and 189 (9.5%) participants, respectively. Measurement of carotid intima-media thickness (IMT), brachial-ankle pulse wave velocity (baPWV), clearance of creatinine, and microalbuminuria were associated with orthostatic hypotension; measurement of IMT and baPWV were associated with orthostatic hypertension in a cruse model. After adjustment, IMT [odds ratio (OR), 95% confidence interval (CI) per one-SD increment: 1.385, 1.052-1.823; P = 0.02], baPWV (OR = 1.627, 95% CI: 1.041-2.544; P = 0.033) and microalbuminuria (OR = 1.401, 95% CI: 1.002-1.958; P = 0.049) were still associated with orthostatic hypotension, while orthostatic hypertension was only associated with IMT (OR = 1.730, 95% CI: 1.143-2.618; P = 0.009). CONCLUSIONS: Orthostatic hypotension seems to be independently correlated with increased carotid atherosclerosis, arterial stiffness and renal damage in subjects over 60 years old. Orthostatic hypertension correlates with carotid atherosclerosis only.

Disordered gut microbiota and alterations in metabolic patterns are associated with atrial fibrillation.

BACKGROUND: With the establishment of the heart-gut axis concept, accumulating studies suggest that the gut microbiome plays an important role in the pathogenesis of cardiovascular diseases. Yet, little evidence has been reported in characterizing the gut microbiota shift in atrial fibrillation. METHODS: We include the result of the global alterations that occur in the intestinal microbiota in a cohort of 50 patients with atrial fibrillation and 50 matched controls based on a strategy of metagenomic and metabolomic analyses. RESULTS: The alterations include a dramatic elevation in microbial diversity and a specific perturbation of gut microbiota composition. Overgrowth of Ruminococcus, Streptococcus, and Enterococcus, as well as reduction of Faecalibacterium, Alistipes, Oscillibacter, and Bilophila were detected in patients with atrial fibrillation. A gut microbial function imbalance and correlated metabolic pattern changes were observed with atrial fibrillation in both fecal and serum samples. The differential gut microbiome signatures could be used to identify patients with atrial fibrillation. CONCLUSIONS: Our findings characterize the disordered gut microbiota and microbial metabolite profiles in atrial fibrillation. Further research could determine whether intervention strategies targeting intestinal microbiome composition might be useful to counteract the progression of atrial fibrillation.

Dysbiotic gut microbes may contribute to hypertension by limiting vitamin D production.

BACKGROUND: Accumulating studies have suggested that gut microbiota (GM) dysbiosis and vitamin D3 deficiency each play an important role during the progression of hypertension (HTN). However, few studies have characterized the underlying interaction between GM shift and vitamin D3 deficiency in HTN patients. HYPOTHESIS: This study aimed to evaluate the possible crosstalk between GM dysbiosis and vitamin D deficiency in the pathogenesis of HTN. METHODS: In a cohort of 34 HTN patients and 15 healthy controls, we analyzed the fecal microbiota products, GM composition, and the interaction between GM and vitamin D3. RESULTS: Vitamin D3 was significantly decreased in feces of HTN patients (P = .006, vs controls) and was correlated with altered GM, including decreased Shannon index (R2 = 0.1296, P = .0111) and Pielou evenness (R2 = 0.1509, P = .0058). Moreover, vitamin D3 positively correlated with HTN-reduced bacterial genera, including Subdoligranulum (R2 = 0.181, P = .0023), Ruminiclostridium (R2 = 0.1217, P = .014), Intestinimonas (R2 = 0.2036, P = .0011), Pseudoflavonifractor (R2 = 0.1014, P = .0257), Paenibacillus (R2 = 0.089, P = .0373), and Marvinbryantia (R2 = 0.08173, P = .0464). Partial least squares structural equation modeling showed that 27.7% of the total effect of gut microbiome on HTN was mediated by limiting vitamin D production. Finally, receiver operating characteristic curve analysis revealed the predictive capacity of differential gut microbiome signatures and decreased vitamin D3 to distinguish HTN patients (AUC = 0.749, P = .006). CONCLUSIONS: Our findings suggest that the GM dysbiosis contributing to the development of HTN might be partially mediated by vitamin D3 deficiency. Future studies involving the underlying mechanism and intervention strategies targeting microbiome composition and vitamin D3 to counteract the progression of HTN are warranted.

Correlation between clinic, cumulative, 24h-ambulatory systolic blood pressure, and chronic kidney damage in Chinese elderly.

The aim of this study was to investigate whether clinic, cumulative, and 24h ambulatory systolic blood pressure (SBP) was associated with chronic kidney damage, defind as estimated glomerular filtration rate (eGFR) <60 ml/(min·1.73 m2) and/or microalbuminuria ≥30 mg/L, and, if so, which measurement of SBP is more associated with chronic kidney damage in Chinese elderly. A total of 1207 participants older than 60 years old were included in the final analysis. Clinical blood pressure, cumulative blood pressure exposure was calculated and ambulatory 24h blood pressure was assessed. Multiple logistic regression analysis showed that the clinic (p < .001), cumulative (p = .033), 24h average (p < .001), daytime (p = .001) and nighttime SBP (p = .001) were respectively associated with lower eGFR, and cumulative (p = .008), 24 average (p < .001), daytime (p < .001), and nighttime SBP (p < .001) were the risk factors of microalbuminuria. The degree of correlation were strongest between 24h average SBP and chronic kidney damage (odds ratio, 1.78; 95% confidence interval, 1.46-2.15; p < .001), clinic SBP and eGFR (odds ratio, 1.57; 95% confidence interval, 1.13-2.17; p = .007), nighttime SBP and microalbuminuria (odds ratio, 1.45; 95% confidence interval, 1.05-2.00; p = .024). The likelihood ratio test demonstrated that the introduction of 24h average SBP will improve the goodness of fit of the clinic SBP model(p < .05), while the introduction of cumulative SBP exposure has no such effect(p > .05). Cumulative SBP exposure seems inferior to other measurement in indentifying chronic kidney damage, including decreased GFR and microalbuminuria.

Progress in Therapies for Myocardial Ischemia Reperfusion Injury.

BACKGROUND: Experimental studies of acute myocardial infarction have revealed that up to half of the final infarct size may be due to reperfusion injury rather than the initial ischemic incident. Research over the past three decades has deepened our understanding of the molecular mechanisms underlying ischemic reperfusion injury and several therapeutic strategies to decrease the incidence and severity of reperfusion injury have been explored. OBJECTIVE: To discuss the promising therapies and future perspectives on methods to attenuate myocardial reperfusion injury. RESULTS: Existing therapies that address reperfusion can be divided into two major groups comprising nonpharmacological and pharmacological interventions. Myriad pharmacological and nonpharmacological approaches to reduce lethal reperfusion injury have been employed. Although many initial clinical studies were negative, more recent proof-of-concept clinical trials are promising. To date, the most encouraging results are with ischemic postconditioning, remote ischemic preconditioning, ANP, adenosine, cyclosporine and exenatide. CONCLUSION: Studies demonstrate that nonpharmacological and pharmacological conditioning can be used together as part of a multifaceted approach to improve clinical outcomes in patients with ischemic heart disease.

Positive Expression of Human Cytomegalovirus Phosphoprotein 65 in Atherosclerosis.

Previous studies showed that human cytomegalovirus (HCMV) is associated with atherosclerosis. However, local vascular atherosclerosis related HCMV infection and protein expression remain unclear. This study aimed to assess the relationship between HCMV infection and atherosclerosis. Formalin-fixed, paraffin-embedded peripheral artery specimens were obtained from 15 patients with atherosclerosis undergoing vascular surgery from 2008 to 2010 at Zhongnan Hospital, Wuhan University. Pathological analyses were carried out after hematoxylin and eosin (H&E) and Masson trichrome staining. In situ hybridization and immunohistochemistry with two different monoclonal antibodies were employed to detect HCMV nucleic acids and proteins, respectively. H&E and Masson trichrome staining showed homogeneous extracellular matrix in femoral artery, while smooth muscle fibers were interlaced with collagen fibers; in carotid artery, inflammatory cell infiltration, foam cell vascular change, cholesterol crystals, and layered collagen fibers were observed. In situ hybridization showed no expression of HCMV nucleic acids in all 15 cases. Immunohistochemical staining for protein immediate-early protein (IE1 72) was negative in all cases, while phosphoprotein 65 (pp65) expression was detected in 14 cases. A high rate of positive pp65 signals was found in patients with atherosclerosis, suggesting that local HCMV infection may be associated with the pathogenesis of atherosclerosis. Further studies on this relationship are warranted.

Vascular endothelial function of patients with stable coronary artery disease.

OBJECTIVES: To evaluate vascular endothelial function and contributing factors in coronary heart disease (CHD) patients. METHODS: One hundred twenty six CHD outpatients were randomly recruited. Reactive hyperemia index (RHI) <1.67 indicates endothelial dysfunction. Correlation between RHI and different biochemical parameters was evaluated. RESULTS: RHI in patients receiving statins treatment was significantly higher than patients without statins treatment (P<0.05). RHI in patients with more than 3 risk factors for CHD was also markedly lower than that in patients with ≤2 risk factors (P<0.05). Patients with lesions at several branches of coronary artery had a markedly lower RHI when compared with those with coronary lesions at a single branch (P<0.05). For patients without statins treatment, RHI increased significantly after statins treatment for 1 month (P=0.01). In patients with endothelial dysfunction, FBG, HbA1C, hs-CRP and Hcy were significantly higher than those in patients with normal endothelial function (P<0.05 for all). Smokers with CHD had a remarkably lower RHI when compared with non-smokers (P<0.05). CONCLUSIONS: Smoking, FBG, HbA1C, Hcy and hs-CRP are significantly associated with endothelial dysfunction. Endothelial dysfunction is also related to the numbers of risk factors for CHD, degree of coronary lesions and statins. Statins treatment may significantly improve the endothelial function of CHD patients.