Cenário Disfuncional dos Principais Componentes Responsáveis pelo Equilíbrio do Trânsito de Cálcio Miocárdico na Insuficiência Cardíaca Induzida por Estenose Aórtica

Silva, Vitor Loureiro da; Souza, Sérgio Luiz Borges de; Mota, Gustavo Augusto Ferreira; Campos, Dijon Henrique Salomé de; Melo, Alexandre Barroso; Vileigas, Danielle Fernandes; Sant’Ana, Paula Grippa; Coelho, Priscila Murucci; Bazan, Silméia Garcia Zanati; Leopoldo, André Soares; Cicogna, Antônio Carlos

doi:10.36660/abc.20200618

Cited by 5 publications

(5 citation statements)

References 39 publications

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“…The magnitude of systolic and diastolic cardiac dysfunction and the structural changes verified in the echocardiographic exams after 18 and 28 weeks of the experimental protocol are in agreement with previous studies [11,12,[27][28][29][30][31][32][33]. The structural adequacy, evidenced by cardiac hypertrophy after a period of aortic constriction, is not functional, presenting a pathological characteristic.…”

Section: Discussionsupporting

confidence: 89%

“…The cardiac contractile performance was evaluated by studying isolated papillary muscles from the LV as previously described [27,64]. The following mechanical parameters were measured during isometric contraction: maximum developed tension (DT; g/mm 2 ), maximum rate of tension development (+dT/dt; g/mm 2 /s), and decline (−dT/dt; g/mm 2 /s).…”

Section: Isolated Papillary Muscle Assaymentioning

confidence: 99%

“…Under anesthesia, rats from each group were euthanized, and the hearts were quickly removed by median thoracotomy and enzymatically isolated as previously described [27]. Briefly, the hearts were cannulated, and retrograde perfusion of the aorta was performed in the Langendorff system (37 • C) with a modified isolation digestion buffer solution (DB), a calcium-free solution containing 0.1 mM ethylene glycol-bis (ß-aminoethyl ether)-N, N, N , N -tetraacetic acid (EGTA), and N-[2-hydro-ethyl]-piperazine-N -[2-ethanesulfonic acid] (HEPES) equilibrated with 5% CO 2 and 95% O 2 for ~3 to 5 min.…”

Section: Cardiomyocyte Contractilitymentioning

confidence: 99%

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Aerobic Exercise Training Improves Calcium Handling and Cardiac Function in Rats with Heart Failure Resulting from Aortic Stenosis

Silva

Mota

Souza

et al. 2023

IJMS

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Aerobic exercise training (AET) has been used to manage heart disease. AET may totally or partially restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis (AoS). This study aimed to evaluate the impact of AET on Ca2+ handling and cardiac function in rats with heart failure due to AoS. Wistar rats were distributed into two groups: control (Sham; n = 61) and aortic stenosis (AoS; n = 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. The cardiac function was analyzed by echocardiogram, isolated papillary muscles, and isolated cardiomyocytes. During assays of isolated papillary muscles and isolated cardiomyocytes, the Ca2+ concentrations were evaluated. The expression of regulatory proteins for diastolic Ca2+ was assessed via Western Blot. AET attenuated the diastolic dysfunction and improved the systolic function. AoS-ET animals presented an enhanced response to post-rest contraction and SERCA2a and L-type Ca2+ channel blockage compared to the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented an alteration in the protein expression of SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity and myofilament responsiveness to Ca2+ and improved the cellular Ca2+ influx mechanism, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with AoS and heart failure.

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Section: Discussionsupporting

confidence: 89%

Section: Isolated Papillary Muscle Assaymentioning

confidence: 99%

Section: Cardiomyocyte Contractilitymentioning

confidence: 99%

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Aerobic Exercise Training Improves Calcium Handling and Cardiac Function in Rats with Heart Failure Resulting from Aortic Stenosis

Silva

Mota

Souza

et al. 2023

IJMS

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“…AS was surgically induced as previously described (Mazeto et al, 2021; Sant'Ana et al, 2018; Silva et al, 2022). Briefly, rats were anesthetized with a mixture of ketamine hydrochloride (50 mg/kg; i.p.)…”

Section: Methodsmentioning

confidence: 99%

“…The heart, in response to several stimuli, undergoes cardiac remodeling, defined as alterations in genome expression, which results in molecular, cellular, and interstitial changes, and clinically manifests as changes in heart size, shape, and function (Cohn et al, 2000). The rodent aortic stenosis (AS) model has been extensively used to induce cardiac remodeling, characterized by left ventricular (LV) hypertrophy, diastolic and systolic dysfunction, and HF (Mazeto et al, 2021; Sant'Ana et al, 2018, 2023; Silva et al, 2022). The mechanisms related to functional impairment in the AS heart are complex and not fully elucidated; alterations in cardiomyocytes, myocardium, and cardiac chambers are involved (Hartupee & Mann, 2017).…”

Section: Introductionmentioning

confidence: 99%

Myocardial proteome changes in aortic stenosis rats subjected to long‐term aerobic exercise

Mota,

de Souza,

Vileigas

et al. 2024

Journal Cellular Physiology

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The effects of exercise training (ET) on the heart of aortic stenosis (AS) rats are controversial and the mechanisms involved in alterations induced by ET have been poorly clarified. In this study, we analyzed the myocardial proteome to identify proteins modulated by moderate‐intensity aerobic ET in rats with chronic supravalvular AS. Wistar rats were divided into four groups: sedentary control (C‐Sed), exercised control (C‐Ex), sedentary aortic stenosis (AS‐Sed), and exercised AS (AS‐Ex). ET consisted of five treadmill running sessions per week for 16 weeks. Statistical analysis was performed by ANOVA or Kruskal–Wallis and Goodman tests. Results were discussed at a significance level of 5%. At the end of the experiment, AS‐Ex rats had higher functional capacity, lower blood lactate concentration, and better cardiac structural and left ventricular (LV) functional parameters than the AS‐Sed. Myocardial proteome analysis showed that AS‐Sed had higher relative protein abundance related to the glycolytic pathway, oxidative stress, and inflammation, and lower relative protein abundance related to beta‐oxidation than C‐Sed. AS‐Ex had higher abundance of one protein related to mitochondrial biogenesis and lower relative protein abundance associated with oxidative stress and inflammation than AS‐Sed. Proteomic data were validated for proteins related to lipid and glycolytic metabolism. Chronic pressure overload changes the abundance of myocardial proteins that are mainly involved in lipid and glycolytic energy metabolism in rats. Moderate‐intensity aerobic training attenuates changes in proteins related to oxidative stress and inflammation and increases the COX4I1 protein, related to mitochondrial biogenesis. Protein changes are combined with improved functional capacity, cardiac remodeling, and LV function in AS rats.

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Aerobic Exercise Training Improves Calcium Handling and Cardiac Function in Rats with Heart Failure Resulting from Aortic Stenosis

Silva¹,

Mota²,

Souza³

et al. 2023

Preprint

View full text Add to dashboard Cite

Aerobic exercise training (AET) has been used in the management of heart disease. AET may, totally or partially, restore the activity and/or expression of proteins that regulate calcium (Ca2+) handling, optimize intracellular Ca2+ flow, and attenuate cardiac functional impairment in failing hearts. However, the literature presents conflicting data regarding the effects of AET on Ca2+ transit and cardiac function in rats with heart failure resulting from aortic stenosis. The objective of this study was to evaluate the effects of AET on calcium handling and cardiac function in rats with heart failure due to aortic stenosis. Wistar rats were distributed into two groups: control (Sham; n= 61) and aortic stenosis (AoS; n= 44). After 18 weeks, the groups were redistributed into: non-exposed to exercise training (Sham, n = 28 and AoS, n = 22) and trained (Sham-ET, n = 33 and AoS-ET, n = 22) for 10 weeks. Treadmill exercise training was performed with a velocity equivalent to the lactate threshold. Echocardiogram, isolated papillary muscle, and isolated cardiomyocyte analyzed cardiac function. During isolated papillary muscle assay and isolated cardimyocyte was evaluated Ca2+. The expression of regulatory proteins of diastolic Ca2+ was analyzed via Western Blot. AET attenuated the diastolic dysfunction and benefited the systolic function. AoS-ET animals presented better response to post-rest contraction, and SERCA2a and L-type Ca2+ channels blocked than the AoS. Furthermore, AET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS-ET animals. AoS animals presented alteration in the protein expression of the SERCA2a and NCX, and AET restored SERCA2a and NCX levels near normal values. Therefore, AET increased SERCA2a activity, improved the cellular Ca2+ influx mechanism, and increased myofilament responsiveness to Ca2+, attenuating cardiac dysfunction at cellular, tissue, and chamber levels in animals with aortic stenosis and heart failure.

show abstract

Cenário Disfuncional dos Principais Componentes Responsáveis pelo Equilíbrio do Trânsito de Cálcio Miocárdico na Insuficiência Cardíaca Induzida por Estenose Aórtica

Cited by 5 publications

References 39 publications

Aerobic Exercise Training Improves Calcium Handling and Cardiac Function in Rats with Heart Failure Resulting from Aortic Stenosis

Aerobic Exercise Training Improves Calcium Handling and Cardiac Function in Rats with Heart Failure Resulting from Aortic Stenosis

Myocardial proteome changes in aortic stenosis rats subjected to long‐term aerobic exercise

Aerobic Exercise Training Improves Calcium Handling and Cardiac Function in Rats with Heart Failure Resulting from Aortic Stenosis

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