Long-term consumption of Western diet contributes to endothelial dysfunction and aortic remodeling in rats: Implication of Rho-kinase signaling

Abstract Background Lipoprotein apheresis (LA) is considered as an add-on therapy for patients with familial hypercholesterolemia (FH). We aimed to analyze the data collected in the last 15 years from FH patients treated with LA, to elucidate the benefit of this procedure with respect to plasma lipids, biomarkers of inflammation, and endothelial dysfunction and soluble endoglin. Results 14 patients (10 heterozygous FH patients (HeFH), 4 homozygous FH patients (HoFH)) were treated by long-term lipoprotein apheresis. Lipid levels were examined, and ELISA detected biomarkers of inflammation and soluble endoglin. Paired tests were used for intergroup comparisons, and a linear regression model served to estimate the influence of the number of days patients were treated with LA on the studied parameters. LA treatment was associated with a significant decrease of total cholesterol (TC), LDL-C, HDL-C, and apoB, in both HeFH and HoFH patients, after single apheresis and in a long-term period during the monitored interval of 15 years. Biomarkers of inflammation and endothelial dysfunction were reduced for soluble endoglin, hsCRP, and MCP-1, and sP-selectin after each procedure in some HeFH and HoFH patients. Conclusions LA treatment up to 15 years, reduced cholesterol levels, levels of biomarkers related to endothelial dysfunction, and inflammation not only after each procedure but also in the long-term evaluation in FH patients. We propose that long-term LA treatment improves lipid profile and endothelial dysfunction in familial hypercholesterolemia patients, suggesting a promising improvement in cardiovascular prognosis in most FH patients.

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Endothelial dysfunction in obstructive sleep apnea patients

Sleep And Breathing ◽

10.1007/s11325-021-02382-4 ◽

2021 ◽

Author(s):

Michał Harańczyk ◽

Małgorzata Konieczyńska ◽

Wojciech Płazak

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Endothelial Dysfunction ◽

Right Ventricular ◽

Contractile Function ◽

Sleep Apnea Syndrome ◽

Apnea Hypopnea Index ◽

Endothelin 1 ◽

Obstructive Sleep

Abstract Purpose Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular diseases. The aim of the study was to assess the influence of OSAS on endothelial dysfunction and thrombosis biomarkers and to evaluate the effect of treatment with continuous positive airway pressure (CPAP) on biomarker levels. Methods NT-proBNP, sICAM-1, endothelin-1, von Willebrand factor, D-dimers, and thrombin-antithrombin complex (TAT) were measured in 50 patients diagnosed with moderate-to-severe OSAS. All patients underwent transthoracic echocardiography, and 38 months after the inclusion, 16 CPAP users and 22 non-CPAP users were reassessed. Results Sleep-related indices of apnea-hypopnea index (AHI) and mean SpO2 were associated with higher sICAM-1 levels (AHI < 30: 7.3 ± 4.7 vs. AHI ≥ 30: 19.5 ± 19.4 mg/ml, p = 0.04; SpO2 ≥ 90%: 11.9 ± 9.3 vs. SpO2 < 90%: 23.6 ± 25.8, p = 0.04). sICAM-1 levels were significantly higher in obese patients, particularly with BMI ≥ 40. Plasma levels of TAT were significantly correlated with the increased right ventricular size (right ventricular diameter ≤ 37 mm: 0.86 ± 0.70 vs. > 37 mm: 1.96 ± 1.20 ng/ml, p = 0.04). Endothelin-1 levels were higher in patients with decreased right ventricular function (right ventricle TDI-derived S′ ≥ 12 cm/s: 11.5 ± 10.9 vs. < 12 cm/s: 26.0 ± 13.2 pg/ml, p = 0.04). An increase in NT-proBNP was related to impaired parameters of the right ventricular contractile function. There were no correlations between long-term CPAP therapy and the levels of biomarkers. Conclusion Severe OSAS influences endothelial damage as manifested by an increase in sICAM-1 levels. Changes in right ventricular structure and function, observed mainly in patients with higher TAT and endothelin-1 levels, are also manifested by an increase in NT-proBNP levels. Long-term CPAP treatment does not seem to influence biomarkers in patients with moderate-to-severe OSAS, which may help to explain the lack of influence of CPAP on cardiovascular risk reduction.

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Endothelial Dysfunction, Atherosclerosis, and Increase of von Willebrand Factor and Factor VIII: A Randomized Controlled Trial in Swine

Thrombosis and Haemostasis ◽

10.1055/s-0040-1722185 ◽

2021 ◽

Author(s):

Ferdows Atiq ◽

Jens van de Wouw ◽

Oana Sorop ◽

Ilkka Heinonen ◽

Moniek P. M. de Maat ◽

...

Keyword(s):

Cardiovascular Disease ◽

Randomized Controlled Trial ◽

Endothelial Dysfunction ◽

Controlled Trial ◽

Short Term ◽

Randomized Controlled ◽

Von Willebrand ◽

Willebrand Factor

AbstractIt is well known that high von Willebrand factor (VWF) and factor VIII (FVIII) levels are associated with an increased risk of cardiovascular disease. It is still debated whether VWF and FVIII are biomarkers of endothelial dysfunction and atherosclerosis or whether they have a direct causative role. Therefore, we aimed to unravel the pathophysiological pathways of increased VWF and FVIII levels associated with cardiovascular risk factors. First, we performed a randomized controlled trial in 34 Göttingen miniswine. Diabetes mellitus (DM) was induced with streptozotocin and hypercholesterolemia (HC) via a high-fat diet in 18 swine (DM + HC), while 16 healthy swine served as controls. After 5 months of follow-up, FVIII activity (FVIII:C) was significantly higher in DM + HC swine (5.85 IU/mL [5.00–6.81]) compared with controls (4.57 [3.76–5.40], p = 0.010), whereas VWF antigen (VWF:Ag) was similar (respectively 0.34 IU/mL [0.28–0.39] vs. 0.34 [0.31–0.38], p = 0.644). DM + HC swine had no endothelial dysfunction or atherosclerosis during this short-term follow-up. Subsequently, we performed a long-term (15 months) longitudinal cohort study in 10 Landrace–Yorkshire swine, in five of which HC and in five combined DM + HC were induced. VWF:Ag was higher at 15 months compared with 9 months in HC (0.37 [0.32–0.42] vs. 0.27 [0.23–0.40], p = 0.042) and DM + HC (0.33 [0.32–0.37] vs. 0.25 [0.24–0.33], p = 0.042). Both long-term groups had endothelial dysfunction compared with controls and atherosclerosis after 15 months. In conclusion, short-term hyperglycemia and dyslipidemia increase FVIII, independent of VWF. Long-term DM and HC increase VWF via endothelial dysfunction and atherosclerosis. Therefore, VWF seems to be a biomarker for advanced cardiovascular disease.

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Apple polyphenols decrease endothelial dysfunction and atherosclerosis in ApoE mice fed with chronic Western diet

Archives of Cardiovascular Diseases Supplements ◽

10.1016/j.acvdsp.2019.02.020 ◽

2019 ◽

Vol 11 (2) ◽

pp. 190

Author(s):

G. Bolea ◽

C. Philouze ◽

S. Risdon ◽

M. Dubois ◽

A. Humberclaude ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Western Diet

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877 ATTENUATED RHOA/RHO-KINASE SIGNALING IN THE PENIS OF TRANSGENIC SICKLE CELL MICE

The Journal of Urology ◽

10.1016/j.juro.2010.02.1633 ◽

2010 ◽

Vol 183 (4S) ◽

Cited By ~ 1

Author(s):

Trinity Bivalacqua ◽

Ashley Ross ◽

Travis Strong ◽

Milena Gebska ◽

Blijana Musicki ◽

...

Keyword(s):

Sickle Cell ◽

Rho Kinase ◽

Kinase Signaling

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The atypical structure and function of newborn arterial endothelium is mediated by Rho/Rho kinase signaling

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00327.2014 ◽

2014 ◽

Vol 307 (4) ◽

pp. H628-H632 ◽

Cited By ~ 10

Author(s):

Sheila Flavahan ◽

Nicholas A. Flavahan

Keyword(s):

Laser Scanning ◽

Rho Kinase ◽

Laser Scanning Microscopy ◽

Scanning Microscopy ◽

Stress Fibers ◽

Light Chains ◽

Myosin Light Chains ◽

Kinase Signaling ◽

No Donor ◽

Kinase Inhibition

Endothelium of fetal or newborn arteries is atypical, displaying actin stress fibers and reduced nitric oxide (NO)-mediated dilatation. This study tested the hypothesis that Rho/Rho kinase signaling, which promotes endothelial stress fibers and inhibits endothelial dilatation, contributed to this phenotype. Carotid arteries were isolated from newborn [ postnatal day 1 (P1)], P7, and P21 mice. Endothelial dilatation to acetylcholine (pressure myograph) was minimal at P1, increased at P7, and further increased at P21. Inhibition of Rho (C3 transferase) or Rho kinase (Y27632, fasudil) significantly increased dilatation to acetylcholine in P1 arteries but had no effect in P7 or P21 arteries. After inhibition of NO synthase ( NG-nitro-l-arginine methyl ester), Rho kinase inhibition no longer increased acetylcholine responses in P1 arteries. Rho kinase inhibition did not affect dilatation to the NO donor DEA-NONOate. The endothelial actin cytoskeleton was labeled with phalloidin and visualized by laser-scanning microscopy. In P1 arteries, the endothelium had prominent transcytoplasmic stress fibers, whereas in P7 and P21 arteries, the actin fibers had a significantly reduced intensity and were restricted to cell borders. Phosphorylation of myosin light chains, a Rho kinase substrate, was highest in P1 endothelium and significantly reduced in P7 and P21 endothelium (laser-scanning microscopy). In P1 arteries, inhibition of Rho (C3 transferase) or Rho kinase (Y27632) significantly reduced the intensity of actin fibers, which were restricted to cell borders. Similarly, in P1 arteries, Rho inhibition significantly reduced endothelial levels of phosphorylated myosin light chains. These results indicate that the atypical function and morphology of newborn endothelium is mediated by Rho/Rho kinase signaling.

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