Temporal relationship between systemic endothelial dysfunction and alterations in erythrocyte function in a murine model of chronic heart failure.

Autor:	Mohaissen T; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland.; Jagiellonian University Medical College, Faculty of Pharmacy, 9 Medyczna St., 30-688, Krakow, Poland., Proniewski B; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland., Targosz-Korecka M; Jagiellonian University Medical College, Faculty of Physics, Institute of Astronomy and Applied Computer Science, a11 Lojasiewicza St., 30-348 Krakow, Poland., Bar A; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland., Kij A; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland., Bulat K; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland., Wajda A; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland.; Jagiellonian University, Faculty of Chemistry, 2 Gronostajowa St., 30-387 Krakow, Poland., Blat A; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland.; Jagiellonian University, Faculty of Chemistry, 2 Gronostajowa St., 30-387 Krakow, Poland., Matyjaszczyk-Gwarda K; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland.; Jagiellonian University Medical College, Faculty of Pharmacy, 9 Medyczna St., 30-688, Krakow, Poland., Grosicki M; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland., Tworzydlo A; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland., Sternak M; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland., Wojnar-Lason K; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland.; Jagiellonian University Medical College, Faculty of Medicine, Chair of Pharmacology, 16 Grzegorzecka St., 31-531 Krakow, Poland., Rodrigues-Diez R; Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPaz), Departamento de Farmacología, Facultad de Medicina, C/Arzobispo Morcillo 4, Madrid, 28029, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), C/Arzobispo Morcillo 4, 28029, Madrid, Spain., Kubisiak A; Jagiellonian University Medical College, Faculty of Physics, Institute of Astronomy and Applied Computer Science, 11 Lojasiewicza St., 30-348 Krakow, Poland., Briones A; Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPaz), Departamento de Farmacología, Facultad de Medicina, C/Arzobispo Morcillo 4, Madrid, 28029, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), C/Arzobispo Morcillo 4, 28029, Madrid, Spain., Marzec KM; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland., Chlopicki S; Jagiellonian University, Jagiellonian Center for Experimental Therapeutics (JCET), 14 Bobrzynskiego St., 30-348 Krakow, Poland.; Jagiellonian University Medical College, Faculty of Medicine, Chair of Pharmacology, 16 Grzegorzecka St., 31-531 Krakow, Poland.
Jazyk:	angličtina
Zdroj:	Cardiovascular research [Cardiovasc Res] 2022 Sep 20; Vol. 118 (12), pp. 2610-2624.
DOI:	10.1093/cvr/cvab306
Abstrakt:	Aims: Endothelial dysfunction (ED) and red blood cell distribution width (RDW) are both prognostic factors in heart failure (HF), but the relationship between them is not clear. In this study, we used a unique mouse model of chronic HF driven by cardiomyocyte-specific overexpression of activated Gαq protein (Tgαq*44 mice) to characterize the relationship between the development of peripheral ED and the occurrence of structural nanomechanical and biochemical changes in red blood cells (RBCs). Methods and Results: Systemic ED was detected in vivo in 8-month-old Tgαq*44 mice, as evidenced by impaired acetylcholine-induced vasodilation in the aorta and increased endothelial permeability in the brachiocephalic artery. ED in the aorta was associated with impaired nitric oxide (NO) production in the aorta and diminished systemic NO bioavailability. ED in the aorta was also characterized by increased superoxide and eicosanoid production. In 4- to 6-month-old Tgαq*44 mice, RBC size and membrane composition displayed alterations that did not result in significant changes in their nanomechanical and functional properties. However, 8-month-old Tgαq*44 mice presented greatly accentuated structural and size changes and increased RBC stiffness. In 12-month-old Tgαq*44 mice, the erythropathy was featured by severely altered RBC shape and elasticity, increased RDW, impaired RBC deformability, and increased oxidative stress (gluthatione (GSH)/glutathione disulfide (GSSG) ratio). Moreover, RBCs taken from 12-month-old Tgαq*44 mice, but not from 12-month-old FVB mice, coincubated with aortic rings from FVB mice, induced impaired endothelium-dependent vasodilation and this effect was partially reversed by an arginase inhibitor [2(S)-amino-6-boronohexanoic acid]. Conclusion: In the Tgαq*44 murine model of HF, systemic ED accelerates erythropathy and, conversely, erythropathy may contribute to ED. These results suggest that erythropathy may be regarded as a marker and a mediator of systemic ED in HF. RBC arginase and possibly other RBC-mediated mechanisms may represent novel therapeutic targets for systemic ED in HF. Competing Interests: Conflict of interest: none declared. (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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