Association of genetic, biochemical and functional markers of the condition of the vascular endothelium in chronic heart failure with mid-range ejection fraction

The aim of this study was to analyse genetic (polymorphism 4a/4b gene NOS3), biochemical (endothelin-1) and functional (endothelial function coefficient) markers of a condition of vascular endothelium in patients (n = 65) with chronic heart failure (CHF) with mid-range ejection fraction (40–49%), depending of the stage of the disease and identify the presence of associations between the analyzed markers. Somatically healthy people (n = 65) were examined as a control group. A decrease in the value of the endothelial function coefficient and an increase in the production of endothelin-1 in all groups of patients compared with somatically healthy people were revealed. The severity of these changes was greater in groups of patients with more severe stage of the disease. The analysis of polymorphism 4a/4b gene NOS3 in patients with CHF revealed a statistically significant predominance of the number of patients with a more severe stage of the disease among of patients with polymorphism 4a/4b. Patients with polymorphism 4a/4b had a statistically significant lower value of the endothelial function coefficient and a higher level of endothelin-1 compared patients with polymorphism 4b/4b. Thus, polymorphism 4a/4b is characterized by a deeper lesion of the vascular endothelium in patients with CHF with mid-range ejection fraction and the development of more severe stages of the disease. The obtained data can be used in the aspect of personalized medicine.

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Abstract 1884: Rosuvastatin Activates Circulating Stem and Progenitor Cells, Promotes Endogenous Tissue Regeneration, and Improves Central Hemodynamics in Patients With Chronic Heart Failure

Circulation ◽

10.1161/circ.116.suppl_16.ii_404-a ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Sandra Erbs ◽

Ephraim B Beck ◽

Axel Linke ◽

Volker Adams ◽

Robert Höllriegel ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Endothelial Function ◽

Progenitor Cells ◽

Tissue Regeneration ◽

Capillary Density ◽

Central Hemodynamics ◽

Stem And Progenitor Cells

Endogenous regeneration is impaired in patients (pts) with chronic heart failure (CHF), which results in peripheral, but also central hemodynamic alterations. Statins are known to promote stem cell release and enhance phosphorylation of the survival kinase AKT, which is associated with an increased cardiomyocyte contractility. Therefore, the present study aimed to investigate the effects of rosuvastatin on number and function of stem and circulating progenitor cells (CPC), their contribution to tissue neovascularization, and its impact on endothelial function and central hemodynamics in pts with CHF. Methods: Forty-two pts with CHF (EF 30±1%; n=12 ischemic, and n=30 dilative cardiomyopathy) were randomized to 12 weeks (wks) of 40 mg rosuvastatin daily or placebo therapy (P) in a double-blind manner. At begin (B) and at 12 wks, the number of circulating CD34 + stem cells and CD34/KDR + CPCs was measured, functional capacity of CPCs was assessed by migration and matrigel assay, and capillary density of skeletal muscle (SM) was quantified. Muscular phosphorylation levels of AKT were determined. Flow-mediated dilatation (FMD) was measured by high-resolution ultrasound and ejection fraction (EF) assessed by echocardiography. Results: Rosuvastatin increased the number of CPCs by +132% (p<0.05 vs P), improved their migratory capacity by +83% and their integrative capacity by +91% (p<0.05 vs P), respectively. FMD recovered from +197±25 μm at B to +478±50 μm at 12 wks in the rosuvastatin group. The rosuvastatin-mediated increase in circulating CD34 + cells was closely correlated to the improvement in FMD (r=0.70, p<0.01) and the augmentation in capillary density of SM (r=0.76, p<0.01). Rosuvastatin enhanced muscular AKT phosphorylation 2.5fold, which was associated with a gain in EF by + 8±1% (p<0.05 vs P). All parameters remained unchanged in the placebo group. Conclusion: In pts with CHF, rosuvastatin improves left-ventricular ejection fraction, promotes skeletal muscle neovascularization, and enhances endothelial function, partially through activation of circulating stem and progenitor cells. Therefore, rosuvastatin might be considered as a therapeutic strategy to induce endogenous tissue regeneration and improve central hemodynamics in CHF.

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Analysis of the reactivity of the endothelium of microvessels of the skin in chronic heart failure

Regional blood circulation and microcirculation ◽

10.24884/1682-6655-2017-16-4-50-55 ◽

2017 ◽

Vol 16 (4) ◽

pp. 50-55 ◽

Cited By ~ 1

Author(s):

O. S. Polunina ◽

L. P. Voronina ◽

E. A. Polunina ◽

I. V. Sevostyanova

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Vascular Endothelium ◽

Contractile Function ◽

Microvascular Endothelium ◽

Doppler Flowmetry ◽

Reduced Ejection Fraction ◽

Leading Role ◽

Myocardial Contractile

Introduction and purpose. The leading role in the pathogenesis of chronic heart failure (CHF) belongs to disturbances in the vascular endothelium. The aim of this work is the identification and analysis of the responses of the microvascular endothelium in patients with CHF, depending on the ejection fraction. Methods. We have examined 280 patients with CHF. Analysis of the reactivity of the endothelium of microvessels was carried out using laser Doppler flowmetry. Results. We have identified 3 types of response of the microvascular endothelium, thus all responses were decrement. Patients with CHF with reduced ejection fraction of the left ventricle was the predominant hyporeactive-decrement type response of the vascular endothelium. Conclusions. Results indicate torpidity of microvascular endothelium and the unidirectionality of the processes state changes of the vascular endothelium with a reduction in myocardial contractile function.

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