Nanoscale Study of Calcium Handling Remodeling in Right Ventricular Cardiomyocytes Following Pulmonary Hypertension.

Autor: Medvedev R; From the Dipartimento di Cardiochirurgia, Università degli Studi di Verona, Ospedale Borgo Trento, Italy (R.M., G.F.).; National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom (R.M., J.L.S.-A., A.A.-L., E.D., V.B.A.S., B.W.-S., J.G.).; Humanitas Clinical and Research Center, Rozzano, Italy (R.M., T.S., M.M.)., Sanchez-Alonso JL; National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom (R.M., J.L.S.-A., A.A.-L., E.D., V.B.A.S., B.W.-S., J.G.)., Alvarez-Laviada A; National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom (R.M., J.L.S.-A., A.A.-L., E.D., V.B.A.S., B.W.-S., J.G.)., Rossi S; Dipartimento di Medicina e Chirurgia, Università degli Studi di Parma, Italy (S.R., M.M.)., Dries E; National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom (R.M., J.L.S.-A., A.A.-L., E.D., V.B.A.S., B.W.-S., J.G.).; Lab of Experimental Cardiology, University of Leuven, Belgium (E.D.)., Schorn T; Humanitas Clinical and Research Center, Rozzano, Italy (R.M., T.S., M.M.)., Abdul-Salam VB; National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom (R.M., J.L.S.-A., A.A.-L., E.D., V.B.A.S., B.W.-S., J.G.)., Trayanova N; Department of Biomedical Engineering and Alliance for Cardiovascular Diagnostic and Treatment Innovation; Johns Hopkins University; Baltimore, MD (N.T.)., Wojciak-Stothard B; National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom (R.M., J.L.S.-A., A.A.-L., E.D., V.B.A.S., B.W.-S., J.G.)., Miragoli M; Dipartimento di Medicina e Chirurgia, Università degli Studi di Parma, Italy (S.R., M.M.)., Faggian G, Gorelik J; National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom (R.M., J.L.S.-A., A.A.-L., E.D., V.B.A.S., B.W.-S., J.G.).
Jazyk: angličtina
Zdroj: Hypertension (Dallas, Tex. : 1979) [Hypertension] 2021 Feb; Vol. 77 (2), pp. 605-616. Date of Electronic Publication: 2020 Dec 28.
DOI: 10.1161/HYPERTENSIONAHA.120.14858
Abstrakt: Pulmonary hypertension is a complex disorder characterized by pulmonary vascular remodeling and right ventricular hypertrophy, leading to right heart failure. The mechanisms underlying this process are not well understood. We hypothesize that the structural remodeling occurring in the cardiomyocytes of the right ventricle affects the cytosolic Ca 2+ handling leading to arrhythmias. After 12 days of monocrotaline-induced pulmonary hypertension in rats, epicardial mapping showed electrical remodeling in both ventricles. In myocytes isolated from the hypertensive rats, a combination of high-speed camera and confocal line-scan documented a prolongation of Ca 2+ transients along with a higher local Ca 2+ -release activity. These Ca 2+ transients were less synchronous than in controls, likely due to disorganized transverse-axial tubular system. In fact, following pulmonary hypertension, hypertrophied right ventricular myocytes showed significantly reduced number of transverse tubules and increased number of axial tubules; however, Stimulation Emission Depletion microscopy demonstrated that the colocalization of L-type Ca 2+ channels and RyR2 (ryanodine receptor 2) remained unchanged. Finally, Stimulation Emission Depletion microscopy and super-resolution scanning patch-clamp analysis uncovered a decrease in the density of active L-type Ca 2+ channels in right ventricular myocytes with an elevated open probability of the T-tubule anchored channels. This may represent a general mechanism of how nanoscale structural changes at the early stage of pulmonary hypertension impact on the development of the end stage failing phenotype in the right ventricle.
Databáze: MEDLINE
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