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001-es BibID:	BIBFORM064197
Első szerző:	Kovács Árpád (kardiológus)
Cím:	Renin overexpression leads to increased titin-based stiffness contributing to diastolic dysfunction in hypertensive mRen2 rats / Árpád Kovács, Gábor Á. Fülöp, Andrea Kovács, Tamás Csípő, Beáta Bódi, Dániel Priksz, Béla Juhász, Lívia Beke, Zoltán Hendrik, Gábor Méhes, Henk L. Granzier, István Édes, Miklós Fagyas, Zoltán Papp, Judit Barta, Attila Tóth
Dátum:	2016
ISSN:	0363-6135
Megjegyzések:	Hypertension (HTN) is a major risk factor for heart failure. We investigated the influence of HTN on cardiac contraction and relaxation in transgenic renin overexpressing rats (carrying mouse Ren-2 renin gene, mRen2, n = 6). Blood pressure (BP) was measured. Cardiac contractility was characterized by echocardiography, cellular force measurements, and biochemical assays were applied to reveal molecular mechanisms. Sprague-Dawley (SD) rats (n = 6) were used as controls. Transgenic rats had higher circulating renin activity and lower cardiac angiotensin-converting enzyme two levels. Systolic BP was elevated in mRen2 rats (235.11 ? 5.32 vs. 127.03 ? 7.56 mmHg in SD, P < 0.05), resulting in increased left ventricular (LV) weight/body weight ratio (4.05 ? 0.09 vs. 2.77 ? 0.08 mg/g in SD, P < 0.05). Transgenic renin expression had no effect on the systolic parameters, such as LV ejection fraction, cardiomyocyte Ca(2+)-activated force, and Ca(2+) sensitivity of force production. In contrast, diastolic dysfunction was observed in mRen2 compared with SD rats: early and late LV diastolic filling ratio (E/A) was lower (1.14 ? 0.04 vs. 1.87 ? 0.08, P < 0.05), LV isovolumetric relaxation time was longer (43.85 ? 0.89 vs. 28.55 ? 1.33 ms, P < 0.05), cardiomyocyte passive tension was higher (1.74 ? 0.06 vs. 1.28 ? 0.18 kN/m(2), P < 0.05), and lung weight/body weight ratio was increased (6.47 ? 0.24 vs. 5.78 ? 0.19 mg/g, P < 0.05), as was left atrial weight/body weight ratio (0.21 ? 0.03 vs. 0.14 ? 0.03 mg/g, P < 0.05). Hyperphosphorylation of titin at Ser-12742 within the PEVK domain and a twofold overexpression of protein kinase C-? in mRen2 rats were detected. Our data suggest a link between the activation of renin-angiotensin-aldosterone system and increased titin-based stiffness through phosphorylation of titin's PEVK element, contributing to diastolic dysfunction.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk hypertension passive stiffness renin-angiotensin-aldosterone system RAAS diastolic dysfunction titin phosphorylation
Megjelenés:	American Journal Of Physiology-Heart And Circulatory Physiology. - 310 : 11 (2016), p. H1671-H1682. -
További szerzők:	Fülöp Gábor Áron (1988-) (általános orvos) Kovács Andrea (1974-) (neurológus) Csípő Tamás (1990-) Bódi Beáta (1989-) (molekuláris biológus) Priksz Dániel (1989-) (farmakológus) Juhász Béla (1978-) (kísérletes farmakológus) Beke Lívia Hendrik Zoltán (1986-) (orvos) Méhes Gábor (1966-) (patológus) Granzier, Henk L. Édes István (1952-) (kardiológus) Fagyas Miklós (1984-) (orvos) Papp Zoltán (1965-) (kardiológus, élettanász) Barta Judit (1975-) (kardiológus) Tóth Attila (1971-) (biológus)
Pályázati támogatás:	PD116212 OTKA K109083 OTKA K116940 OTKA MEDIA FP7
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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