SERCA-2a is involved in the right ventricular function following myocardial infarction in rats

Fernandes, Aurélia Araújo; Ribeiro, Rogério Faustino; Moura, Viviane; Siman, Fabiana Deise; Dias, Fernanda Moura Vargas; Zoghaib, Jorge; Vassallo, Paula Frizera; Vassallo, Dalton Valentim; Stefanon, Ivanita

doi:10.1016/j.lfs.2015.01.010

Cited by 17 publications

(12 citation statements)

References 31 publications

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“…Consistent with a previous study demonstrating that Serca2 upregulation post‐MI may aid in preservation of ventricular function (Fernandes et al. ), our study suggests that timely resolution of inflammation may improve ventricular function through increased Serca2 expression.…”

Section: Discussionsupporting

confidence: 92%

The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models

Hitscherich

Xie

et al. 2019

Physiol Rep

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Following myocardial infarction ( MI ), myocardial inflammation plays a crucial role in the pathogenesis of MI injury and macrophages are among the key cells activated during the initial phases of the host response regulating the healing process. While macrophages have emerged as attractive effectors in tissue injury and repair, the contribution of macrophages on cardiac cell function and survival is not fully understood due to complexity of the in vivo inflammatory microenvironment. Understanding the key cells involved and how they communicate with one another is of paramount importance for the development of effective clinical treatments. Here, novel in vitro myocardial inflammation models were developed to examine how both direct and indirect interactions with polarized macrophage subsets present in the post‐ MI microenvironment affect cardiomyocyte function. The indirect model using conditioned medium from polarized macrophage subsets allowed examination of the effects of macrophage‐derived factors on stem cell‐derived cardiomyocyte function for up to 3 days. The results from the indirect model demonstrated that pro‐inflammatory macrophage‐derived factors led to a significant downregulation of cardiac troponin T ( cTnT ) and sarcoplasmic/endoplasmic reticulum calcium ATP ase (Serca2) gene expression. It also demonstrated that inhibition of macrophage‐secreted matricellular protein, osteopontin ( OPN ), led to a significant decrease in cardiomyocyte store‐operated calcium entry ( SOCE ). In the direct model, stem cell‐derived cardiomyocytes were co‐cultured with polarized macrophage subsets for up to 3 days. It was demonstrated that anti‐inflammatory macrophages significantly increased cardiomyocyte Ca 2+ fractional release while macrophages independent of their subtypes led to significant downregulation of SOCE response in cardiomyocytes. This study describes simplified and controlled in vitro myocardial inflammation models, which allow examination of potential beneficial and deleterious effects of macrophages on cardiomyocytes and vise versa. This can lead to our improved understanding of the inflammatory microenvironment post‐ MI , otherwise difficult to directly investigate in vivo or by using currently available in vitro models.

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Section: Discussionsupporting

confidence: 92%

The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models

Hitscherich

Xie

et al. 2019

Physiol Rep

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“…This RV dysfunction may be related to the molecular mechanisms involved in calcium transport (Opie ; Fernandes et al . ). Several proteins such as ryanodine receptor (RyR), phospholamban (PLB) and Ca 2+ ATPase of the sarcoplasmic reticulum (SERCA2a), regulate calcium homeostasis in the heart muscle and are essential for its proper functioning (Opie ; Lima‐Leopoldo et al .…”

mentioning

confidence: 97%

“…In the development of PAH RV dysfunction precedes heart failure (HF) and this occurs when there are alterations in the relaxation and/or contraction of the heart muscle without promoting fluid retention or exercise intolerance (Cohn et al 2000;Pacagnelli et al 2014). This RV dysfunction may be related to the molecular mechanisms involved in calcium transport (Opie 1998;Fernandes et al 2015). Several proteins such as ryanodine receptor (RyR), phospholamban (PLB) and Ca 2+ ATPase of the sarcoplasmic reticulum (SERCA2a), regulate calcium homeostasis in the heart muscle and are essential for its proper functioning (Opie 1998;Lima-Leopoldo et al 2013).…”

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confidence: 99%

Preventive aerobic training exerts a cardioprotective effect on rats treated with monocrotaline

Pacagnelli

Sabela

Okoshi

et al. 2016

Int J Experimental Path

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Pulmonary arterial hypertension (PAH) is a chronic disease which causes overload to the right ventricle. The effect of preventive training on cardiac remodelling in this condition is still unknown. This study aimed to evaluate the influence of preventive training on hypertrophy, heart function and gene expression of calcium transport proteins in rats with monocrotaline-induced PAH. Thirty-two male Wistar rats were randomly divided into four groups: S, sedentary control; T, trained control; SM, sedentary monocrotaline; and TM, trained monocrotaline. The preventive training protocol was performed on a treadmill for 13 weeks, five times/week. The first two weeks were adopted for adaptation to training with gradual increases in speed/time. The speed of the physical training from the third to tenth weeks was gradually increased from 0.9 to 1.1 km/h for 60 min. Next, monocrotaline was applied (60 mg/kg) to induce PAH and lactate threshold analysis performed to determine the training speeds. The training speed of the TM group in the following two weeks was 0.8 km/h for 60 min and the T = 0.9 km/h for 60 min; in the final two weeks, both groups trained at the same speed and duration 0.9 km/h, 60 min. Cardiac function was assessed through echocardiography, ventricular hypertrophy through histomorphometric analysis and gene expression through RT-qPCR. Right cardiac function assessed through the peak flow velocity was SM = 75.5 cm/s vs. TM = 92.0 cm/s (P = 0.001), and ventricular hypertrophy was SM = 106.4 μm² vs. TM = 77.7 μm² (P = 0.004). There was a decrease in the gene expression of ryanodine S = 1.12 au vs. SM = 0.60 au (P = 0.02) without alterations due to training. Thus, we conclude that prior physical training exerts a cardioprotective effect on the right ventricle in the monocrotaline rat model.

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“… 19 – 21 SERCA2a dysfunction as a causal factor for intracellular Ca 2+ overload and cardiac contractile dysfunction in the setting of MI has been well documented by many research groups. 22 – 24 Yet, how SERCA2a expression and function are regulated during MI remained poorly understood.…”

mentioning

confidence: 99%

LncRNA ZFAS1 as a SERCA2a Inhibitor to Cause Intracellular Ca ²⁺ Overload and Contractile Dysfunction in a Mouse Model of Myocardial Infarction

Zhang

Jiao

Sun

et al. 2018

Circulation Research

173

142

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SERCA-2a is involved in the right ventricular function following myocardial infarction in rats

Abstract: Increased SERCA-2a protein expression may play a role in the preservation of RV function post-MI. Therefore, therapeutic strategies that attempt to increase SERCA protein expression levels may be useful for the treatment of HF.

Cited by 17 publications

References 31 publications

The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models

The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models

Preventive aerobic training exerts a cardioprotective effect on rats treated with monocrotaline

LncRNA ZFAS1 as a SERCA2a Inhibitor to Cause Intracellular Ca ²⁺ Overload and Contractile Dysfunction in a Mouse Model of Myocardial Infarction

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SERCA-2a is involved in the right ventricular function following myocardial infarction in rats

Abstract: Increased SERCA-2a protein expression may play a role in the preservation of RV function post-MI. Therefore, therapeutic strategies that attempt to increase SERCA protein expression levels may be useful for the treatment of HF.

Cited by 17 publications

References 31 publications

The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models

The effects of macrophages on cardiomyocyte calcium‐handling function using in vitro culture models

Preventive aerobic training exerts a cardioprotective effect on rats treated with monocrotaline

LncRNA ZFAS1 as a SERCA2a Inhibitor to Cause Intracellular Ca 2+ Overload and Contractile Dysfunction in a Mouse Model of Myocardial Infarction

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LncRNA ZFAS1 as a SERCA2a Inhibitor to Cause Intracellular Ca ²⁺ Overload and Contractile Dysfunction in a Mouse Model of Myocardial Infarction