Myocardial reverse remodeling after pressure unloading is associated with maintained cardiac mechanoenergetics in a rat model of left ventricular hypertrophy

Ruppert, Mihály; Korkmaz‐Icöz, Sevil; Li, Shiliang; Németh, Balázs Tamás; Hegedűs, Péter; Brlecic, Paige; Mátyás, Csaba; Zorn, Markus; Merkely, Béla; Kretzler, Matthias; Radovits, Tamás; Szabó, Gábor

doi:10.1152/ajpheart.00085.2016

Cited by 19 publications

(19 citation statements)

References 46 publications

(64 reference statements)

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“…Moreover, recent evidence also showed that mechano‐energetics recovery contributes to myocardial reverse remodeling with reductions in load (Ruppert et al. ). Although myocardial adaptations to left ventricular assist devices (LVAD) support indicate substantial potential for structural, functional, and molecular plasticity within severely diseased hearts, sustained myocardial recovery after LVAD removal has been reported in only a small percent of cases, although higher rates may be possible (Hellawell and Margulies ).…”

Section: Discussionmentioning

confidence: 99%

Histological evidence for reversible cardiomyocyte changes and serum cardiac troponin T elevation after exercise in rats

Nie

George

Duan

et al. 2016

Physiological Reports

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This study characterized cardiac troponin T (cTnT) appearance and associated histological evidence of reversible or irreversible changes in myocardial ultrastructure, determined via electron microscopy, in rats undertaking isoproterenol (ISO) infusion or an endurance exercise challenge. Male rats were randomized into ISO and exercise groups. In ISO trials rats were killed 5 h (ISO‐5H) and 24 h (ISO‐REC19H) after a single ISO or saline injection (SAL‐5H; SAL‐REC19H). In the exercise trials rats were killed before, as a control (EXE‐CON), immediately after (EXE‐END5H) and 19 h after (EXE‐REC19H) a 5‐h bout of swimming with 5% body weight attached to their tail. Serum cTnT was quantified by electrochemiluminescence, and myocardial samples in ISO‐REC19H, EXE‐REC19H and SAL‐REC19H were harvested for assessment of specific mitochondrial injury scores using electron‐microscopy. cTnT was undetectable in all control animals (SAL‐5H/SAL‐REC19H and EXE‐CON). cTnT increased in all animals after ISO and exercise but the response was significantly higher (P < 0.05) at ISO‐5H (median [range]: 2.60 [1.76–6.18] μg · L−1) than at EXE‐END5H (median [range]: 0.05 [0.02–0.14] μg · L−1). cTnT returned to baseline at EXE‐REC19H, but had not completely recovered at ISO‐REC19H (median [range]: 0.17 [0.09–1.22] μg · L−1). Mitochondrial “injury scores” were significantly higher (P < 0.05) in ISO‐REC19H compared to EXE‐REC19H and SAL‐REC19H, with no difference between EXE‐REC19H and SAL‐REC19H. Mitochondria from EXE‐REC19H appeared aggregated in nonlinear clusters in a small number of scans. These findings suggest that acute exercise‐induced appearance of cTnT in this animal model is only associated with reversible changes in cardiomyocyte structure.

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Section: Discussionmentioning

confidence: 99%

Histological evidence for reversible cardiomyocyte changes and serum cardiac troponin T elevation after exercise in rats

Nie

George

Duan

et al. 2016

Physiological Reports

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“…Partial occlusion of the ascending aorta is a common experimental method to induce PO, cardiac hypertrophy, and HF. Although previous studies have shown thickening of the aortic wall, adventitial hyperplasia, collagen deposition, and inflammatory changes, the molecular signaling pathways responsible for this remodeling have not been identified [ 18 , 19 , 20 , 21 , 22 , 23 ]. Importantly, Gal-3 overexpression increased the collagen type I protein levels in VSMCs, and Gal-3 blockade reduces aortic fibrosis and inflammation in other pathological conditions showing its key role in vascular damage [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Galectin-3 Blockade in Vascular and Aortic Valve Alterations in an Experimental Pressure Overload Model

Ibarrola

Martínez‐Martínez

Sádaba

et al. 2017

IJMS

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Galectin-3 (Gal-3) is involved in cardiovascular fibrosis and aortic valve (AV) calcification. We hypothesized that Gal-3 pharmacological inhibition with modified citrus pectin (MCP) could reduce aortic and AV remodeling in normotensive rats with pressure overload (PO). Six weeks after aortic constriction, vascular Gal-3 expression was up-regulated in male Wistar rats. Gal-3 overexpression was accompanied by an increase in the aortic media layer thickness, enhanced total collagen, and augmented expression of fibrotic mediators. Further, vascular inflammatory markers as well as inflammatory cells content were greater in aorta from PO rats. MCP treatment (100 mg/kg/day) prevented the increase in Gal-3, media thickness, fibrosis, and inflammation in the aorta of PO rats. Gal-3 levels were higher in AVs from PO rats. This paralleled enhanced AV fibrosis, inflammation, as well as greater expression of calcification markers. MCP treatment prevented the increase in Gal-3 as well as fibrosis, inflammation, and calcification in AVs. Overall, Gal-3 is overexpressed in aorta and AVs from PO rats. Gal-3 pharmacological inhibition blocks aortic and AV remodeling in experimental PO. Gal-3 could be a new therapeutic approach to delay the progression and the development of aortic remodeling and AV calcification in PO.

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“…anaesthesia as previously described1650. After recovering from anaesthesia and on the first and second postoperative day, all animals received meloxicam (1.5 mg/kg p.o.)…”

Section: Methodsmentioning

confidence: 99%

Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload

Németh

Mátyás

Oláh

et al. 2016

Sci Rep

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Pathologic myocardial hypertrophy develops when the heart is chronically pressure-overloaded. Elevated intracellular cGMP-levels have been reported to prevent the development of pathologic myocardial hypertrophy, therefore we investigated the effects of chronic activation of the cGMP producing enzyme, soluble guanylate cyclase by Cinaciguat in a rat model of pressure overload-induced cardiac hypertrophy. Abdominal aortic banding (AAB) was used to evoke pressure overload-induced cardiac hypertrophy in male Wistar rats. Sham operated animals served as controls. Experimental and control groups were treated with 10 mg/kg/day Cinaciguat (Cin) or placebo (Co) p.o. for six weeks, respectively. Pathologic myocardial hypertrophy was present in the AABCo group following 6 weeks of pressure overload of the heart, evidenced by increased relative heart weight, average cardiomyocyte diameter, collagen content and apoptosis. Cinaciguat did not significantly alter blood pressure, but effectively attenuated all features of pathologic myocardial hypertrophy, and normalized functional changes, such as the increase in contractility following AAB. Our results demonstrate that chronic enhancement of cGMP signalling by pharmacological activation of sGC might be a novel therapeutic approach in the prevention of pathologic myocardial hypertrophy.

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Myocardial reverse remodeling after pressure unloading is associated with maintained cardiac mechanoenergetics in a rat model of left ventricular hypertrophy

Cited by 19 publications

References 46 publications

Histological evidence for reversible cardiomyocyte changes and serum cardiac troponin T elevation after exercise in rats

Histological evidence for reversible cardiomyocyte changes and serum cardiac troponin T elevation after exercise in rats

Beneficial Effects of Galectin-3 Blockade in Vascular and Aortic Valve Alterations in an Experimental Pressure Overload Model

Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload

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