Impaired coronary capillary hemodynamics with decreased glycocalyx thickness and irregular inner wall remodeling in right ventricle of pulmonary hypertensive rats

We hypothesized that coronary capillary function is impaired with a decreased glycocalyx layer and uneven inner wall remodeling in right ventricles that are hypertrophied due to pulmonary hypertension (PH). Five-week-old male Sprague-Dawley rats were divided into 2 groups (PH: n=25, control: n=27). In the PH group, Monocrotaline (60 mg/kg SC) was administrated at 5 weeks. Coronary capillary hemodynamics was visualized in vivo at 8 weeks of age using our high-resolution intravital videomicrosopy, and RBC velocities in RV capillaries were evaluated, along with capillary diameters. Configuration of the capillary cast was assessed by a confocal laser scanning microscope. The thickness of the glycocalyx on the capillary endothelial surface was evaluated with Alcian blue 8GX by electron microscopy. RV systolic pressure increased in PH (by 142%, p<0.01). The diameters of capillaries were uneven in PH (coefficient of variation of diameters along capillary trees; 24±8% vs. 11±3%, p<0.05). The thickness of the glycocalyx in PH was less than half that of control (0.20±0.05 vs. 0.45±0.14 μm, p<0.05). RBC velocity was decreased in PH (820±110 vs. 1,100±230 μm/sec, p<0.05). The capillary flow reduction in PH may be closely related to the changes in the glycocalyx and vessel irregularity, resulting in insufficient oxygen supply to the heart

Elevated serum adipocyte fatty acid-binding protein concentrations are independently associated with renal dysfunction in patients with stable angina pectoris

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) is associated with cardiovascular events. Adipocyte fatty acid-binding protein (A-FABP) plays an important role in atherosclerosis. We investigated whether plasma A-FABP is involved in renal function in patients with stable angina pectoris.</p> <p>Methods</p> <p>A total of 221 patients with significant coronary artery stenosis were enrolled after coronary angiography. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m². The severity of coronary stenosis was assessed using a modified Gensini score and coronary angiography. Serum A-FABP levels were determined by enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>Serum A-FABP levels were significantly correlated with both eGFR (r = -0.41, p < 0.01) and the severity of coronary artery stenosis (r = 0.16, p = 0.02), and these relationships remained significant after adjusting for confounding factors. The prevalence of CKD and multi-vessel disease was significantly higher among patients with serum A-FABP levels above the median value of 20.3 ng/ml than among patients with serum A-FABP levels below the median value (57% vs. 27%, p < 0.01 and 64% vs. 48%, p = 0.02, respectively). Multivariate analysis revealed that the presence of three-vessel disease in comparison with single-vessel disease was independently associated with the higher A-FABP (per doubling) (odds ratio; 2.26, 95% confidential interval; 1.28-3.98, p < 0.01) and tended to be associated with the lower eGFR (p = 0.06).</p> <p>Conclusion</p> <p>Serum A-FABP may have a significant role in the interplay between renal dysfunction and coronary atherosclerosis.</p

Single GUV Method Reveals Interaction of Tea Catechin (−)-Epigallocatechin Gallate with Lipid Membranes

Tea catechins, which are flavonoids and the main components of green tea extracts, are thought to have antibacterial and antioxidant activity. Several studies indicate that lipid membranes are one of the targets of the antibacterial activity of catechins. Studies using a suspension of large unilamellar vesicles (LUVs) indicate that catechin causes gradual leakage of internal contents from LUVs. However, the detailed characteristics of the interaction of catechins with lipid membranes remain unclear. In this study, we investigated the interaction of (−)-epigallocatechin gallate (EGCg), a major catechin in tea extract, with single giant unilamellar vesicles (GUVs) of egg phosphatidylcholine (egg PC) using phase-contrast fluorescence microscopy and the single GUV method. We prepared GUVs of lipid membranes of egg PC in a physiological ion concentration (∼150 mM NaCl) using the polyethylene glycol-lipid method. Low concentrations of EGCg at and above 30 μM induced rapid leakage of a fluorescent probe, calcein, from the inside of single egg PC-GUVs; after the leakage, the GUVs changed into small lumps of lipid membranes. On the other hand, phase-contrast microscopic images revealed the detailed process of the EGCg-induced burst of GUVs, the decrease in their diameter, and their transformation into small lumps. The dependence of the fraction of burst GUVs on EGCg concentration was almost the same as that of the fraction of leaked GUV. This correlation strongly indicates that the leakage of calcein from the inside to the outside of the GUV occurred as a result of the burst of the GUV. The fraction of completely leaked GUV and the fraction of the burst GUV increased with time and also increased with increasing EGCg concentration. We compared the EGCg-induced leakage from single GUVs with EGCg-induced leakage from a LUV suspension. The analysis of the EGCg-induced shape changes shows that the binding of EGCg to the external monolayer of the GUV increases its membrane area, inducing an increase in its surface pressure. Small angle x-ray scattering experiments indicate that the intermembrane distance of multilamellar vesicles of PC membrane greatly decreased at EGCg concentrations above the threshold, suggesting that neighboring membranes came in close contact with each other. On the basis of these results, we discuss the mechanism of the EGCg-induced bursting of vesicles