Cardioprotective Effect of Whole Body Periodic Acceleration in Dystrophic Phenotype mdx Rodent

Uryash, Arkady; Mijares, Alfrédo; Estève, É.; Adams, José A.; López, José R.

doi:10.3389/fphys.2021.658042

Cited by 6 publications

(6 citation statements)

References 92 publications

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“…[Ca 2+ ] d is regulated by several mechanisms that controls Ca 2+ influx-efflux and intracellular reuptake that allow the maintenance of [Ca 2+ ] within a physiological range (~100 nM) ( Lopez et al., 2011 ; Mijares et al., 2014 ; Mijares et al., 2020 ). The [Ca 2+ ] d values obtained from CONT cardiomyocytes are in agreement with previous estimates obtained from humans ( Lopez et al., 2011 ; Mijares et al., 2020 ) and non-human ventricular myocytes ( Mijares et al., 2014 ; Uryash et al., 2021a ; Uryash et al., 2021b ) using Ca 2+ -selective microelectrodes and fluorescent Ca 2+ indicator ( Piacentino et al., 2003 ). The abnormal [Ca 2+ ] d in cardiomyocytes from infected mice (chronic>acute>early acute) agree with a similar dysfunction observed in cardiomyocytes obtained from Chagas patients and could potentially promote arrhythmias, similar to those observed in patients with Chagas cardiomyopathy ( Benziger et al., 2017 ; Almeida et al., 2018 ).…”

Section: Discussionsupporting

confidence: 89%

“…Calcium is essential in the regulation of cardiac contractility, and defective intracellular Ca 2+ homeostasis plays an vital role in the pathogenesis of diverse cardiac diseases ( Houser and Margulies, 2003 ; Lopez et al., 2011 ; Uryash et al., 2021a ; Uryash et al., 2021b ). [Ca 2+ ] d is regulated by several mechanisms that controls Ca 2+ influx-efflux and intracellular reuptake that allow the maintenance of [Ca 2+ ] within a physiological range (~100 nM) ( Lopez et al., 2011 ; Mijares et al., 2014 ; Mijares et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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The Role of the Na+/Ca2+ Exchanger in Aberrant Intracellular Ca2+ in Cardiomyocytes of Chagas-Infected Rodents

López

Linares

Adams

et al. 2022

Front. Cell. Infect. Microbiol.

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Chagas disease is produced by the parasite Trypanosoma cruzi (T. cruzi), which is the leading cause of death and morbidity in Latin America. We have shown that in patients with Chagas cardiomyopathy, there is a chronic elevation of diastolic Ca2+ concentration ([Ca2+]d), associated with deterioration to further address this issue, we explored the role Na+/Ca2+ exchanger (NCX). Experiments were carried out in noninfected C57BL/6 mice and infected with blood-derived trypomastigotes of the T. cruzi Y strain. Anesthetized mice were sacrificed and the cardiomyocytes were enzymatically dissociated. Diastolic [Ca2+] ([Ca2+]d) was measured using Ca2+ selective microelectrodes in cardiomyocytes from control mice (CONT) and cardiomyocytes from T. cruzi infected mice in the early acute phase (EAP) at 20 dpi, in the acute phase (AP) at 40 dpi, and in the chronic phase (CP) at 120 dpi. [Ca2+]d was 1.5-times higher in EAP, 2.6-times in AP, and 3.4-times in CP compared to CONT. Exploring the reverse mode activity of NCX, we replaced extracellular Na+ in equivalent amounts with N-methyl-D-glucamine. Reduction of [Na+]e to 65 mM caused an increase in [Ca2+]d of 1.7 times in cardiomyocytes from CONT mice, 2 times in EAP infected mice, 2.4 times in AP infected mice and 2.8 in CP infected mice. The Na+ free solution caused a further elevation of [Ca2+]d of 2.5 times in cardiomyocytes from CONT, 2.8 times in EAP infected mice, 3.1 times in AP infected mice, and 3.3 times in CP infected mice. Extracellular Ca2+ withdrawal reduced [Ca2+]d in both CONT and cardiomyocytes from Chagas-infected mice and prevented the increase in [Ca2+]d induced by Na+ depletion. Preincubation with 10µM KB-R7943 or in 1µM YM-244769 reduced [Ca2+]d in cardiomyocytes from infected mice, but not control mice. Furthermore, both NCX blockers prevented the increase in [Ca2+]d associated with exposure to a solution without Na+. These results suggest that Ca2+ entry through the reverse NCX mode plays a significant role in the observed [Ca2+]d dyshomeostasis in Chagas infected cardiomyocytes. Additionally, NCX inhibitors may be a viable therapeutic approach for treating patients with Chagas cardiomyopathy.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

The Role of the Na+/Ca2+ Exchanger in Aberrant Intracellular Ca2+ in Cardiomyocytes of Chagas-Infected Rodents

López

Linares

Adams

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Our study found similar results with Dmd mdx‐4Cv hearts releasing significantly more LDH compared to Wt hearts of the same age, regardless of maintained (young) or diminished (middle‐age) cardiac function throughout the load challenge. Several biomarkers can be used to examine cardiac damage in the setting of muscular dystrophy, including LDH (Barnabei & Metzger, 2012 ; Burelle et al., 2010 ; Haffner et al., 2023 ), creatine kinase (Chang et al., 2016 ; Jearawiriyapaisarn et al., 2010 ; Law et al., 2018 ), and Troponin I (De Giorgio et al., 2023 ; Lopez et al., 2017 ; Matsumura et al., 2007 ; Uryash et al., 2021 ). Indeed, there are advantages and disadvantages of each including size (Creatine Kinase preferred) and specificity (Troponin I preferred).…”

Section: Discussionmentioning

confidence: 99%

Right ventricular preload and afterload challenge induces contractile dysfunction and arrhythmia in isolated hearts of dystrophin‐deficient male mice

Behrmann,

Cayton,

Hayden

et al. 2024

Physiological Reports

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Duchenne muscular dystrophy (DMD) is an X‐linked recessive myopathy due to mutations in the dystrophin gene. Diaphragmatic weakness in DMD causes hypoventilation and elevated afterload on the right ventricle (RV). Thus, RV dysfunction in DMD develops early in disease progression. Herein, we deliver a 30‐min sustained RV preload/afterload challenge to isolated hearts of wild‐type (Wt) and dystrophic (Dmdmdx‐4Cv) mice at both young (2–6 month) and middle‐age (8–12 month) to test the hypothesis that the dystrophic RV is susceptible to dysfunction with elevated load. Young dystrophic hearts exhibited greater pressure development than wild type under baseline (Langendorff) conditions, but following RV challenge exhibited similar contractile function as wild type. Following the RV challenge, young dystrophic hearts had an increased incidence of premature ventricular contractions (PVCs) compared to wild type. Hearts of middle‐aged wild‐type and dystrophic mice had similar contractile function during baseline conditions. After RV challenge, hearts of middle‐aged dystrophic mice had severe RV dysfunction and arrhythmias, including ventricular tachycardia. Following the RV load challenge, dystrophic hearts had greater lactate dehydrogenase (LDH) release than wild‐type mice indicative of damage. Our data indicate age‐dependent changes in RV function with load in dystrophin deficiency, highlighting the need to avoid sustained RV load to forestall dysfunction and arrhythmia.

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“…Pulsatile shear stress, as produced by pGz, has been shown to upregulate the protein expression of both nNOs and eNOS, thus increasing NO synthesis and increasing antioxidant expression, including superoxide dismutase, catalase, and total antioxidant capacity [7]. Furthermore, pGz has been shown to significantly decrease [Ca 2+ ] i in muscle cells with abnormal intracellular [Ca 2+ ] [9].…”

Section: Introductionmentioning

confidence: 99%

Enhancing Muscle Intracellular Ca2+ Homeostasis and Glucose Uptake: Passive Pulsatile Shear Stress Treatment in Type 2 Diabetes

Uryash,

Umlas,

Mijares

et al. 2023

Biomedicines

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Type 2 diabetes mellitus (T2D) is a significant global public health problem that has seen a substantial increase in the number of affected individuals in recent decades. In a murine model of T2D (db/db), we found several abnormalities, including aberrant intracellular calcium concentration ([Ca2+]i), decreased glucose transport, increased production of reactive oxygen species (ROS), elevated levels of pro-inflammatory interleukins and creatine phosphokinase (CK), and muscle weakness. Previously, we demonstrated that passive pulsatile shear stress, generated by sinusoidal (headward–forward) motion, using a motion platform that provides periodic acceleration of the whole body in the Z plane (pGz), induces the synthesis of nitric oxide (NO) mediated by constitutive nitric oxide synthase (eNOS and nNOS). We investigated the effect of pGz on db/db a rodent model of T2D. The treatment of db/db mice with pGz resulted in several beneficial effects. It reduced [Ca2+]i overload; enhanced muscle glucose transport; and decreased ROS levels, interleukins, and CK. Furthermore, pGz treatment increased the expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and neuronal nitric oxide synthase (nNOS); reduced inducible nitric oxide synthase (iNOS); and improved muscle strength. The cytoprotective effects of pGz appear to be mediated by NO, since pretreatment with L-NAME, a nonspecific NOS inhibitor, abolished the effects of pGz on [Ca2+]i and ROS production. Our findings suggest that a non-pharmacological strategy such as pGz has therapeutic potential as an adjunct treatment to T2D.

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Cardioprotective Effect of Whole Body Periodic Acceleration in Dystrophic Phenotype mdx Rodent

Cited by 6 publications

References 92 publications

The Role of the Na+/Ca2+ Exchanger in Aberrant Intracellular Ca2+ in Cardiomyocytes of Chagas-Infected Rodents

The Role of the Na+/Ca2+ Exchanger in Aberrant Intracellular Ca2+ in Cardiomyocytes of Chagas-Infected Rodents

Right ventricular preload and afterload challenge induces contractile dysfunction and arrhythmia in isolated hearts of dystrophin‐deficient male mice

Enhancing Muscle Intracellular Ca2+ Homeostasis and Glucose Uptake: Passive Pulsatile Shear Stress Treatment in Type 2 Diabetes

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