Correlation between endothelial dysfunction and redox-potential decreasing in patients with severe form of congestive heart failure

SummaryEndothelial dysfunction and enhanced platelet reactivity in congestive heart failure (CHF) contribute to poor prognosis. CHF patients display an impaired responsiveness to clopidogrel. Fractalkine activates platelets and elevated plasma levels of this chemokine are a feature of CHF. We here addressed the interrelation of fractalkine, platelet reactivity and clopidogrel efficacy in humans and rats with CHF. Fractalkine serum levels determined by ELISA were increased in CHF patients (CHF: 1548 ± 650 pg/ml; Control: 968 ± 575 pg/ml, p<0.01) and following CHF induction in rats (CHF: 1509 ± 753 pg/ ml; Sham: 1181 ± 275 pg/ml, p<0.05). Expression of fractalkine and its receptor CX3CR1 was enhanced in aortas of CHF rats as determined by immunofluorescence microscopy and molecular analysis. Fractalkine significantly aggravated endothelial dysfunction and augmented P-selectin expression on platelets from CHF rats. Platelet surface expression of CX3CR1 was increased in CHF rats, who displayed an impaired response to clopidogrel (platelet reactivity to ADP: CHF 30 ± 22%; Sham: 8 ± 5%, p<0.05). Similarly in humans with CHF, elevated fractalkine levels were accompanied by reduced clopidogrel responsiveness. Patients with high on-clopidogrel treatment platelet P2Y12 reactivity displayed higher fractalkine levels (1525 ± 487 pg/ml) than those with sufficient clopidogrel response (684 ± 315 pg/ml, p<0.01). In conclusion, in CHF fractalkine was increased on the endothelium and in blood serum, and platelet surface- expression of CX3CR1 was enhanced. Fractalkine diminished endothelial function beyond the impairment already observed in CHF and was associated with a reduced responsiveness to the platelet inhibitor clopidogrel. These findings may indicate a novel pathophysiological mechanism contributing to impaired clopidogrel responsiveness in CHF.

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Pharmacological correction of plasma redox potential and endothelial dysfunction in ischemic heart failure

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2012-1-54-58 ◽

2012 ◽

Vol 11 (1) ◽

pp. 54-58 ◽

Cited By ~ 1

Author(s):

O. P. Donetskaya ◽

V. A. Tulupova ◽

N. V. Shuldeshova ◽

M. M. Fedorova

Keyword(s):

Heart Failure ◽

Endothelial Dysfunction ◽

Redox Potential ◽

Standard Therapy ◽

Pyridine Nucleotide ◽

Functional Class ◽

Potential Reduction ◽

Pharmacological Correction ◽

Endothelial Growth Factor ◽

First Time

Aim. To study the role of plasma redox potential reduction in the development of endothelial dysfunction (ED) among patients with chronic heart failure (CHF) and to investigate the potential of its pharmacological correction. Material and methods. This randomised cohort study included 73 patients with CHF, due to coronary heart disease (CHD) and arterial hypertension. Mean age of the participants was 59,2±5,9 years. Functional Class (FC) I CHF was registered in 9 patients, FC II CHF in 21, FC III CHF in 23, and FC IV CHF in 11. After the baseline examination, all participants were randomised into two groups. The main group (MG) received standard therapy plus adenocin (2 ampoules in 70 ml 5% glucose, intravenously) for 10 days. Results. For the first time, the dynamics of redox potential and total pyridine nucleotide levels was assessed in relation to the FC of ischemic CHF. Redox potential reduction preceded the changes in the total pyridine nucleotide levels. In contrast to standard therapy, adenocin increased plasma redox potential and endothelial growth factor levels, while reducing endothelin-1 concentrations and NADPH oxidase activity. Conclusion. Combination therapy with adenocin – a unique medication of reduced NAD form, cardiac glycoside, and inosine, in contrast to standard treatment, significantly increased cellular redox potential in CHF, which could play an important role in angiogenesis stimulation and reverse endothelial remodelling.

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