Clinical Implication of Coronary Tortuosity in Patients with Coronary Artery Disease

Background: Coronary tortuosity (CT) is a common coronary angiography finding. The exact pathogenesis, clinical implication and long-term prognosis of CT are not fully understood. The purpose of this study is to investigate the clinical characteristics of CT in patients with suspected coronary artery disease(CAD) in a Chinese population. Methods: A total of 1010 consecutive patients underwent coronary angiography with complaints of chest pain or related symptoms were included in the present study (544 male, mean age: 64611 years). CT was defined by the finding of $3 bends (defined as$45u change in vessel direction) along main trunk of at least one artery in systole and in diastole. Patients with or without CAD were further divided into CT-positive and CT-negative groups, all patients were followed up for the incidence of major adverse cardiovascular events (MACE) for 2 to 4 years. Results: The prevalence of CT was 39.1 % in this patient cohort and incidence of CT was significantly higher in female patients than that in male patients (OR = 2.603, 95%CI 1.897, 3.607, P,0.001). CT was positively correlated with essential hypertension (OR = 1.533, 95%CI 1.131, 2.076, P = 0.006) and negatively correlated with CAD (OR = 0.755, 95%CI 0.574, 0.994, P = 0.045). MACE during follow up was similar between CAD patients with or without CT. Conclusions: CT is more often seen in females and positively correlated with hypertension and negatively correlated wit

Effect of a 180 mg ticagrelor loading dose on myocardial necrosis in patients undergoing elective percutaneous coronary intervention: A preliminary study

Background: To examine whether a loading dose of ticagrelor on top of clopidogrel reduced postpercutaneous coronary intervention (PCI) myonecrosis. Methods: Seventy seven coronary artery disease patients received a loading dose of 300 mg clopidogrel pre-PCI and were divided into three groups: group TT (n = 36): a loading dose of 180 mg ticagrelor pre-PCI, followed by ticagrelor 90 mg twice daily commencing one day post-PCI; group CT (n = 26): a maintenance dose of ticagrelor 90 mg twice daily; group CC (n = 15): clopidogrel 75 mg daily post- PCI. High sensitivity cardiac troponin T (hs-cTnT) and creatine kinase-MB (CK-MB) were measured pre-PCI and 0 h, 2 h or 24 h post-PCI. Platelet aggregation was measured in a separate cohort of 54 coronary artery disease patients (35 diabetic and 19 non-diabetic patients). Results: There were no significant differences in hs-cTnT and CK-MB concentration among the three groups. In group TT, diabetic patients had significant higher Δhs-cTnT2h–0h than non-diabetic patients. In the second cohort, although baseline platelet aggregation was higher in diabetic than non-diabetic patients, platelet aggregation was comparable between diabetic and non-diabetic patients at 0 and 2 h post-PCI. Conclusions: This study indicates that a loading dose of ticagrelor does not significantly reduce post- PCI myonecrosis. Diabetes is associated with more post-PCI myonecrosis. A loading dose of ticagrelor effectively reduces platelet aggregation in diabetic patients.

Anti-inflammatory Effects of α7-nicotinic ACh Receptors are Exerted Through Interactions with Adenylyl Cyclase-6

Background and purpose Alpha 7 nicotinic acetylcholine receptors (CHRNA7) suppress inflammation through diverse pathways in immune cells, so is potentially involved in a number of inflammatory diseases. However, the detailed mechanisms underlying CHRNA7’s anti‐inflammatory effects remain elusive. Experimental approach The anti‐inflammatory effects of CHRNA7 agonists in both murine macrophages (RAW 264.7) and bone marrow‐derived macrophages (BMDM) stimulated with LPS were examined. The role of adenylyl cyclase 6 (AC6) in Toll‐like Receptor 4 (TLR4) degradation was explored via overexpression and knockdown. A mouse model of chronic obstructive pulmonary disease was used to confirm key findings. Results Anti‐inflammatory effects of CHRNA7 were largely dependent on AC6 activation, as knockdown of AC6 considerably abnegated the effects of CHRNA7 agonists while AC6 overexpression promoted them. We found that CHRNA7 and AC6 are co‐localized in lipid rafts of macrophages and directly interact. Activation of AC6 led to the promotion of TLR4 degradation. Administration of CHRNA7 agonist PNU‐282987 attenuated pathological and inflammatory end points in a mouse model of chronic obstructive pulmonary disease (COPD). Conclusion and implications CHRNA7 inhibits inflammation through activating AC6 and promoting degradation of TLR4. The use of CHRNA7 agonists may represent a novel therapeutic approach for treating COPD and likely other inflammatory diseases

Weakening and strengthening structures in the Hadley Circulation change under global warming and implications for cloud response and climate sensitivity

It has long been recognized that differences in climate model-simulated cloud feedbacks are a primary source of uncertainties for the model-predicted surface temperature change induced by increasing greenhouse gases such as CO_2. Large-scale circulation broadly determines when and where clouds form and how they evolve. However, the linkage between large-scale circulation change and cloud radiative effect (CRE) change under global warming has not been thoroughly studied. By analyzing 15 climate models, we show that the change of the Hadley Circulation exhibits meridionally varying weakening and strengthening structures, physically consistent with the cloud changes in distinct cloud regimes. The regions that experience a weakening (strengthening) of the zonal-mean circulation account for 54% (46%) of the multimodel-mean top-of-atmosphere (TOA) CRE change integrated over 45°S–40°N. The simulated Hadley Circulation structure changes per degree of surface warming differ greatly between the models, and the intermodel spread in the Hadley Circulation change is well correlated with the intermodel spread in the TOA CRE change. This correlation underscores the close interactions between large-scale circulation and clouds and suggests that the uncertainties of cloud feedbacks and climate sensitivity reside in the intimate coupling between large-scale circulation and clouds. New model performance metrics proposed in this work, which emphasize how models reproduce satellite-observed spatial variations of zonal-mean cloud fraction and relative humidity associated with the Hadley Circulation, indicate that the models closer to the satellite observations tend to have equilibrium climate sensitivity higher than the multimodel mean

Tightening of tropical ascent and high clouds key to precipitation change in a warmer climate

The change of global-mean precipitation under global warming and interannual variability is predominantly controlled by the change of atmospheric longwave radiative cooling. Here we show that tightening of the ascending branch of the Hadley Circulation coupled with a decrease in tropical high cloud fraction is key in modulating precipitation response to surface warming. The magnitude of high cloud shrinkage is a primary contributor to the intermodel spread in the changes of tropical-mean outgoing longwave radiation (OLR) and global-mean precipitation per unit surface warming (dP/dTs) for both interannual variability and global warming. Compared to observations, most Coupled Model Inter-comparison Project Phase 5 models underestimate the rates of interannual tropical-mean dOLR/dTs and global-mean dP/dTs, consistent with the muted tropical high cloud shrinkage. We find that the five models that agree with the observation-based interannual dP/dTs all predict dP/dTs under global warming higher than the ensemble mean dP/dTs from the ∼20 models analysed in this study

Modulation of cardiac resident macrophages immunometabolism upon high-fat-diet feeding in mice

BackgroundA high-fat diet (HFD) contributes to various metabolic disorders and obesity, which are major contributors to cardiovascular disease. As an essential regulator for heart homeostasis, cardiac resident macrophages may go awry and contribute to cardiac pathophysiology upon HFD. Thus, to better understand how HFD induced cardiac dysfunction, this study intends to explore the transcriptional and functional changes in cardiac resident macrophages of HFD mice.MethodsC57BL/6J female mice that were 6 weeks old were fed with HFD or normal chow diet (NCD) for 16 weeks. After an evaluation of cardiac functions by echocardiography, mouse hearts were harvested and cardiac resident CCR2- macrophages were sorted, followed by Smart sequencing. Bioinformatics analysis including GO, KEGG, and GSEA analyses were employed to elucidate transcriptional and functional changes.ResultsHyperlipidemia and obesity were observed easily upon HFD. The mouse hearts also displayed more severe fibrosis and diastolic dysfunction in HFD mice. Smart sequencing and functional analysis revealed metabolic dysfunctions, especially lipid-related genes and pathways. Besides this, antigen-presentation-related gene such as Ctsf and inflammation, particularly for NF-κB signaling and complement cascades, underwent drastic changes in cardiac resident macrophages. GO cellular compartment analysis was also performed and showed specific organelle enrichment trends of the involved genes.ConclusionDysregulated metabolism intertwines with inflammation in cardiac resident macrophages upon HFD feeding in mice, and further research on crosstalk among organelles could shed more light on potential mechanisms

Enhancement of Anti-Hypoxic Activity and Differentiation of Cardiac Stem Cells by Supernatant Fluids from Cultured Macrophages that Phagocytized Dead Mesenchymal Stem Cells

Background: Most mesenchymal stem cells (MSCs) die shortly after transplantation into a myocardial infarcted area. Dead MSCs (dMSCs) are phagocytized by macrophages (pMΦ) in vivo and in vitro; however, the effects of pMΦ on cardiac stem cells (CSCs) remain unknown. Methods: MSCs, CSCs, and macrophages were obtained from bone marrow, hearts, and peritoneal cavity of mice, respectively. dMSCs were harvested after hypoxia for 24 h, and incubated with macrophages (2:1) for another 2 days with or without lipopolysaccharide (LPS, 50 ng/mL) and sorted by flow cytometry to obtain pMΦ. Viability and apoptosis of CSCs were respectively evaluated with the cell counting kit-8 (CCk-8) assay and Annexin V-PE/7-AAD staining at 0, 6, 12, and 24 h of culture with supernatant fluids from macrophages (MΦ), LPS-stimulated macrophages (LPS-pMΦ), pMΦ, and MSCs. GATA-4 and c-TnI expression was measured by flow cytometry on the seventh day. Expression of inflammation and growth factors was assessed by real-time polymerase chain reaction (RT-PCR) in MΦ, LPS-pMΦ, and pMΦ cells. Results: pMΦ expressed higher levels of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β)and lower levels of tumor necrosis factor-α(TNF-α)and IL-6 than LPS-pMΦ, higher levels of growth factors and of GATA-4 and c-TnI at the 7th day, which were similar to those in MSCs. CSCs cultured with supernatant fluids of pMΦ exhibited higher proliferative, anti-hypoxic, and differentiation activities. Conclusion: The supernatant fluids of macrophages that had phagocytized dead MSCs encouraged changes in phenotype and growth factor expression, enhanced proliferation, differentiation, and anti-hypoxic activity of CSCs, which is relevant to understanding the persistent therapeutic effect of MSCs after their massive demise upon transplantation in myocardial infarction. Furthermore, some miRNAs or proteins which were extracted from the supernatant fluids may give us a new insight into the treatment of myocardial infarction in the future