Chemical renal denervation-induced upregulation of the ACE2/Ang (1-7)/Mas axis attenuates blood pressure elevation in spontaneously hypertensive rats

Objective Evidence has shown that the ACE2/Ang (1–7)/Mas axis plays an important role in the control of hypertension. Thus, we hypothesized that chemical renal denervation (RDN) could reduce blood pressure by regulating the ACE2/Ang (1–7)/Mas axis in spontaneously hypertensive rats. Methods Twelve rats were randomly divided into sham group and chemical RDN group. All the rats were sacrificed 4 weeks later. Plasma samples were collected to measure the renin-angiotensin system (RAS) activities and reactive oxygen species levels by radioimmunoassay, chromatometry and ELISA. Paraventricular nucleus (PVN) tissues were collected to examine the expression of the components of the ACE2/Ang (1–7)/Mas axis by western bolt and immunofluorescence. Results The systolic blood pressure (169.33 ± 7.50 vs 182.67 ± 7.00 mmHg, p < .05) and the diastolic blood pressure (97.50 ± 4.68 vs 109.33 ± 4.41 mmHg, p < .05) in the RDN group were obviously lower than the baseline levels, whereas the opposite results were observed in the sham group. The RDN group exhibited a significant reduction in the plasma ROS (91.59 ± 13.12 vs 72.34 ± 11.76 U/ml, p < .05) and NADPH oxidase (171.86 ± 1.14 vs 175.75 ± 1.74 nmol/ml, p < .001) compared with the sham group, while the plasma eNOS (3.47 ± 0.42 vs 2.49 ± 0.51 U/ml, p < .05) and NO (55.92 ± 8.10 vs 43.53 ± 4.58 μmol/L, p < .05) were increased. The expression of the components of the ACE2/Ang (1–7)/Mas axis was upregulated while the expression of the components of the ACE/Ang II/AT1 R axis was downregulated in the plasma and PVN in the RDN group. Conclusion Our findings suggested that the reduction in blood pressure was regulated by chemical RDN-induced upregulation of the components of the ACE2/Ang (1–7)/Mas axis

Feasibility of Quantitative Flow Ratio Virtual Stenting for Guidance of Serial Coronary Lesions Intervention

Background Coronary physiology measurement in serial coronary lesions with multiple stenoses is challenging. Therefore, we evaluated the feasibility of Murray fractal law‐based quantitative flow ratio (μQFR) virtual stenting for guidance of serial coronary lesions intervention. Methods and Results Patients who underwent elective coronary angiography and had 2 serial de novo coronary lesions of 30% to 90% diameter stenosis by visual estimation were prospectively enrolled. μQFR and fractional flow reserve (FFR) were assessed after coronary angiography. In vessels with an FFR ≤0.80, the lesion with the larger pressure gradient was considered to be the primary lesion and treated firstly, followed by FFR measurement. The second lesion was stented when FFR ≤0.80. All μQFR and predicted μQFR after stenting were calculated from diagnostic coronary angiography before interventions, with the analysts masked to the FFR data. A total of 54 patients with 61 target vessels were interrogated. Percutaneous coronary intervention was performed in 44 vessels with FFR ≤0.80. After stenting the primary lesions, 14 nonprimary lesions had FFR ≤0.80 and a second drug‐eluting stent was implanted. There was excellent correlation (r=0.97, P<0.001) and good agreement (mean difference: 0.00±0.03) between baseline μQFR and FFR in identifying flow‐limiting lesions. Per‐vessel diagnostic accuracy of μQFR on de novo lesions was 96.7% (95% CI, 88.7%–99.6%). μQFR and FFR are highly consistent (93.2%) in identifying the primary lesion requiring revascularization. After stenting the primary lesions, per‐vessel diagnostic accuracy of predicted μQFR for identifying the significance of the nonprimary lesion was 90.9%. Predicted residual μQFR with virtual stenting was higher than final FFR (mean difference: 0.05±0.06). Conclusions In vessels with serial coronary lesions, virtual stenting by μQFR can identify the primary flow‐limiting lesion for revascularization

Targeting AMPK signalling pathway with natural medicines for atherosclerosis therapy: an integration of <i>in silico</i> screening and <i>in vitro</i> assay

<p>An integration of virtual screening and kinase assay was reported to identify AMPK kinase inhibitors from various natural medicines.The activation of AMP-activated protein kinase (AMPK) signalling pathway plays a central role in the pathologic progression of atherosclerosis (AS). Targeting the AMPK is thus considered as a potential therapeutics to attenuate AS. Here, we report the establishment of a synthetic pipeline that integrates <i>in silico</i> virtual screening and <i>in vitro</i> kinase assay to discover new lead compounds of AMPK inhibitors. The screening is performed against a large-size pool of structurally diverse natural products, from which a number of compounds are inferred as promising candidates, and few of them are further tested <i>in vitro</i> by using a standard kinase assay protocol to determine their inhibitory potency against AMPK. With this scheme we successfully identify five potent AMPK inhibitors with IC₅₀ values at micromolar level. We also examine the structural basis and molecular mechanism of nonbonded interaction network across the modelled complex interface of AMPK kinase domain with a newly identified natural medicine.</p

Representative Myocardial Perfusion Images of the Left Anterior Descending Coronary Artery (LAD) and Right Coronary Artery (RCA) using both MSCT and SPECT Examination.

<p>3A: MSCT early scanning; 3B: MSCT late scanning; 3C: Stressed thallium-201 (²⁰¹TI)-SPECT imaging; 3D: ^99mTc-MIBI imaging; 3E: ²⁰¹TI-SPECT late resting image.</p

Representative Reconstructed Images of CTO Lesions at the Left Anterior Descending Coronary Artery (LAD) and Right Coronary Artery (RCA).

<p>1A, 1D: Coronary angiography (CAG) image; 1B, 1E: Multiplanar reconstruction images; 1C, 1F: Three-dimensional volume rendering (Tree) image.</p