Search Results (232)

Cardiomyocytes, similarly to cells in various tissues, are responsive to mechanical stress of all types, which is reflected in the significant alterations to their electrophysiological characteristics. This phenomenon, known as mechanoelectric feedback, is based on the work of mechanically gated channels (MGCs) and mechano-sensitive channels (MSCs). Since microgravity (MG) in space, as well as simulated microgravity (SMG), changes the morphological and physiological properties of the heart, it was assumed that this result would be associated with a change in the expression of genes encoding MGCs and MSCs, leading to a change in the synthesis of channel proteins and, ultimately, a change in channel currents during cell stretching. In isolated ventricular cardiomyocytes of rats exposed to SMG for 14 days, the amount of MGCs and MSCs gene transcripts was studied using the RNA sequencing method by normalizing the amount of “raw” reads using the Transcripts Per Kilobase Million (TPM) method. Changes in the level of channel protein, using the example of the MGCs TRPM7, were assessed by the Western blot method, and changes in membrane ion currents in the control and during cardiomyocyte stretching were assessed by the patch-clamp method in the whole-cell configuration. The data obtained demonstrate that SMG results in a multidirectional change in the expression of genes encoding various MGCs and MSCs. At the same time, a decrease in the TPM of the MGCs TRPM7 gene leads to a decrease in the amount of TRPM7 protein. The resulting redistribution in the synthesis of most channel proteins leads to a marked decrease in the sensitivity of the current through MGCs to cell stretching and, ultimately, to a change in the functioning of the heart. Full article

Background/Objectives: Ellagic acid (EA) is a polyphenol found in several fruits and vegetables, including pomegranate, nuts and berries. It exhibits significant health benefits, mainly cardio- and vaso-protective; indeed, EA protects the myocardium against infarction and inhibits cardiac fibrosis. These beneficial effects may be, at least in part, promoted by calcium release from and uptake by the sarcoplasmic reticulum, which are crucial events for cardiac relaxation and contraction. Regardless, the exact mechanism is currently unclear. Methods: A deeper investigation of the role of EA in cardiac contractility and the underlying mechanism has been carried out by using an ex vivo model of isolated and perfused rat heart. Results and Discussion: EA perfusion (100 nM–10 µM) did not influence the coronary flow (CF), suggesting the absence of a vasoactivity, but significantly increased contractility parameters (LVDP and dP/dt). Interestingly, a more marked effect of EA on LVDP and dP/dt values was observed when it was perfused in the presence of AngII. Cyclopiazonic acid (CA) and red ruthenium (RR), specific antagonists of SERCA and RyRs, respectively, were used to explore the contribution of EA when the intracellular calcium handling was altered. In the presence of CA, EA, perfused at increasing concentrations, showed a very modest positive inotropism (significant only at 1 µM). Instead, RR, which significantly compromised all functional parameters, completely masked the effects of EA; furthermore, a marked reduction in CF and a dramatic impact on the positive inotropism occurred. Conclusions: These results demonstrate the positive inotropism of EA on isolated and perfused hearts and suggest that the RyRs may be a main target through which EA plays its effects, since inhibition with RR almost completely blocks the positive inotropism. Full article

Background: The limited regenerative capacity of adult mammalian cardiomyocytes (CMs) poses a significant challenge for cardiac repair following myocardial infarction. In contrast to adult mammals, CMs in zebrafish and newt hearts retain a lifelong capacity for proliferation and cardiac regeneration. Likewise, neonatal mice exhibit a brief postnatal period, during which CMs retain the ability to proliferate and contribute to myocardial repair, which markedly diminishes within the first week of life. Emerging evidence indicates that adult CM cell cycle progression is critically influenced by oxidative stress. Adult mammalian CMs possess a high mitochondrial content to meet their substantial energy demands. However, this also leads to elevated reactive oxygen species (ROS) production, resulting in DNA damage and subsequent cell cycle arrest. We hypothesize that reducing the mitochondrial content in adult CMs will mitigate ROS production, thereby facilitating cell cycle progression. Methods: Adult CMs were isolated from adult rats (≥12 weeks old). To induce mitophagy, adult CMs were transfected with parkin-expressing plasmid and then treated with carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a mitochondrial protonophore, for 7 days. Post-treatment assessments included the quantification of adult CM proliferation, mitochondrial content, and ROS levels. Results: CCCP-treated adult CMs exhibited a significant increase in proliferation markers, including EdU incorporation, KI67, phospho-histone H3, and Aurora B. Furthermore, CCCP treatment significantly reduced the mitochondrial content, as evidenced by decreased MitoTracker, TMRM, and Tom20 staining compared to controls. This was accompanied by electron microscopy analysis, which showed a significant reduction in the mitochondrial number in the adult CM after CCCP treatment. Moreover, our results also demonstrate a marked reduction in oxidative stress, demonstrated by lower 123-dihydro-rhodamine (123-DHR), CellROX signals, and VDAC. Conclusions: Our findings demonstrate that CCCP-mediated mitochondrial depletion reduces oxidative stress and promotes cell cycle re-entry in adult CM. This study provides direct experimental evidence and substantiates the role of elevated mitochondria and ROS levels in adult CM cell cycle exit. Full article

Encephalomyocarditis virus (EMCV) causes sporadic and epizootic outbreaks among various domesticated and non-domesticated animal species worldwide. Although outbreaks are mostly reported in domestic pigs, mortality is reported in elephants, ungulates, nonhuman primates (NHPs), and rodents. Rats of the genus Rattus serve as primary reservoirs and vectors, but alternative infection routes have been proposed. Clinical disease is characterized by acute heart failure in most taxonomic groups, often culminating in rapid death. Due to the rapid progression of the disease, diagnostic confirmation is most commonly obtained postmortem. Pathological examination reveals interstitial lymphohistiocytic myocarditis and multiorgan congestion in most cases. EMCV is often demonstrated with RT-PCR or virus isolation techniques, but other methods, e.g., serology and immunohistochemistry, are available. The rapid progression of EMCV precludes effective therapeutic intervention, though agents such as interferon, verapamil, and curcumol have shown potential efficacy. Preventative strategies are crucial, emphasizing biosecurity measures to mitigate rodent contamination of feed and water. Inactivated vaccines have demonstrated protective efficacy in experimental models involving mice, pigs, and elephants, with analogous immunogenic responses observed in various zoological species. Live attenuated vaccines have conferred protection in pigs and NHPs, albeit with variable seroconversion rates in different species. Full article

Alveolar active sodium transport is essential for clearing edema from airspaces, in a process known as alveolar fluid clearance (AFC). Although it has been reported that atrial natriuretic peptide (ANP) attenuates AFC, little is known about the underlying molecular effects of natriuretic peptides (NPs). Therefore, we examined the contribution of NPs to AFC and their effects as mediators of active sodium transport. By using the isolated liquid-filled lungs model, we investigated the effects of NPs on AFC. The expression of NPs, Na⁺, K⁺-ATPase, and Na⁺ channels was assessed in alveolar epithelial cells. Congestive heart failure (CHF) was induced by using the aortocaval fistula model. ANP and brain NP (BNP) significantly reduced AFC rate from 0.49 ± 0.02 mL/h in sham rats to 0.26 ± 0.013 and 0.19 ± 0.005 in ANP and BNP-treated groups, respectively. These effects were mediated by downregulating the active Na⁺ transport components in the alveolar epithelium while enhancing the ubiquitination and degradation of αENaC in the lungs, as reflected by increased levels of Nedd4-2. In addition, AFC was reduced in compensated CHF rats treated with ANP, while in decompensated CHF, ANP partially restored AFC. In conclusion, NPs regulate AFC in health and CHF. This research could help optimize pharmacological treatments for severe CHF. Full article

Our previous research has shown that SDOs derived from yellow silk cocoons have hypotensive effects on rats in chronic toxicity testing. This study investigated the potential preventative and therapeutic benefits of SDOs on hypertensive rats induced by L-NAME. The experiment involved nine rat groups: (1) normal control, (2) normal + 200 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ BW SDOs, (3) hypertensive (HT) control, (4) HT + 50 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ BW SDOs, (5) HT + 100 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ BW SDOs, (6) HT + 200 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ BW SDOs, (7) HT + enalapril (Ena), (8) HT + soy protein isolate (SPI), and (9) HT + bovine serum albumin (BSA). In the preventative approach, rats received 40 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ of L-NAME with the studied substances during the four-week investigation. SDOs given at doses of 100 and 200 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ BW demonstrated a significant decrease in systolic blood pressure (SBP) without affecting heart rate (HR). In therapeutic studies, 40 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ BW of L-NAME increased SBP in the experimental groups over the first four weeks, resulting in mean SBP values above 150 mmHg. Administering 100 and 200 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ BW SDOs and 100 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ BW SPI significantly reduced SBP. However, SDOs at 200 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ BW exhibited SBP closer to the enalapril group. In functional vascular tests, rats given SDOs at a dose of 200 $\mathrm{m}\mathrm{g} {\mathrm{k}\mathrm{g}}^{-1}$ BW had the highest relaxation and lowest contraction percentages, like the normal control groups. The research found that SDOs may inhibit and manage hypertension in both healthy and hypertensive rats by safeguarding endothelial cells. Full article

Background/Objectives: Pulmonary hypertension is a progressive disease leading to right heart failure. One treatment strategy is to induce vasodilation via the nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate (NO–sGC–cGMP) signaling pathway. There are currently two soluble guanylate cyclase stimulators on the market: Riociguat and vericiguat, with vericiguat having a longer half-life and needing to be taken only once a day. This study investigated whether the pharmacological differences between the drugs affect pulmonary vessels and airways. Methods: The effects of vericiguat and riociguat on pulmonary arteries, veins, and airways were studied using rat precision-cut lung slices (PCLS). Vessels were pretreated with endothelin-1 and airways with serotonin. In isolated perfused lungs (IPL), the effects of sGC stimulation on pulmonary artery pressure (PAP), airway resistance, inflammatory cytokine, and chemokine release were quantified. Results: Riociguat and vericiguat caused pulmonary artery dilation in PCLS. During IPL, riociguat was more effective than vericiguat in reducing PAP with a statistically significant reduction of 10%. Both drugs were potent bronchodilators in preconstricted airways (p < 0.001). Only vericiguat reduced airway resistance during IPL, as shown here for the first time. Both drugs significantly reduced IL-6 and IL-1ß levels, while riociguat also reduced VEGF-A and KC-GRO levels. Conclusions: Riociguat and vericiguat had three main effects in the two rat ex-vivo models: They dilated the pulmonary arteries, induced bronchodilation, and reduced inflammation. These properties could make sGC stimulators useful for treating diseases associated with endothelial dysfunction. In the future, vericiguat may provide an alternative treatment to induce bronchodilation in respiratory diseases. Full article

The dried root of Sanguisorba officinalis L. (commonly known as Diyu) has been studied for its various pharmacological effects, including its antibacterial, antitumor, antioxidant, and anti-inflammatory activities. In the present study, primary cultured vascular endothelial cells (HUVECs) and isolated phenylephrine-precontracted rat thoracic aortic rings were examined to investigate the possible mechanism of a butanol extract of Diyu (BSO) in its vascular relaxant effect. HUVECs treated with BSO produced a significantly higher amount of nitric oxide (NO) compared to the control. However, its production was inhibited by pretreatment with N^G-nitro-L-arginine methylester (L-NAME) or wortmannin. BSO also increased the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt. In the aortic ring, BSO relaxed PE-precontracted rat thoracic aortic rings in a concentration-dependent manner. The absence of the vascular endothelium significantly attenuated BSO-induced vasorelaxation. The non-selective NOS inhibitor, L-NAME, and the selective inhibitor of soluble guanylyl cyclase (sGC), 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ), dramatically inhibited the BSO-induced relaxation effect of the endothelium-intact aortic ring. Ca²⁺-free buffer and intracellular Ca²⁺ homeostasis regulators (TG, Gd³⁺, and 2–APB) inhibited BSO-induced vasorelaxation. In Ca²⁺-free Krebs solution, BSO markedly reduced PE-induced contraction. Vasodilation induced by BSO was significantly inhibited by wortmannin, an inhibitor of Akt. Pretreatment with the non-selective inhibitor of Ca²⁺-activated K⁺ channels (K_Ca), tetraethylammonium (TEA), significantly attenuated the BSO-induced vasorelaxant effect. Furthermore, BSO decreased the systolic blood pressure and heart rate in a concentration-dependent manner in rats. In conclusion, BSO induces vasorelaxation via endothelium-dependent signaling, primarily through the activation of the PI3K-Akt-eNOS-NO signaling pathway in endothelial cells, and the activation of the NO-sGC-cGMP-K⁺ channels pathway in vascular smooth muscle cells. Additionally, store-operated Ca²⁺ entry (SOCE)-eNOS pathways and the inhibition of Ca²⁺ mobilization from intracellular stores contribute to BSO-induced vasorelaxation. Full article

Background: Myocardial injury (MI) is characterized by an increased level of at least one cardiac troponin. Experimental MI can be induced by isoprenaline, a β-adrenergic agonist, and it can lead to heart failure (HF). Liraglutide is glucagon-like 1 peptide receptor agonist used in diabetes management, but it has anti-inflammatory and antioxidative effects, which can be beneficial in treatment of HF. The aim of this study was to investigate the effects of liraglutide on isoprenaline-induced MI and prevention of HF. Methods: Male Wistar albino rats were divided into four groups: Con—received saline the first 2 days + saline the next 7 days; Iso—isoprenaline the first 2 days + saline the next 7 days; Lir—saline the first 2 days + liraglutide the next 7 days; Iso + Lir—isoprenaline the first 2 days + liraglutide the next 7 days. On day 10, blood samples were taken for biochemical analysis and oxidative stress marker evaluation, and hearts were isolated for pathohistological analysis. Cardiac function was assessed by electrocardiography (ECG) and echocardiography (ECHO). Results: Liraglutide treatment significantly attenuated oxidative stress, repaired ECG and ECHO parameters, and mitigated myocardial morphological changes induced by isoprenaline. Conclusions: Liraglutide restores cardiac function in isoprenaline-induced HF. Full article

Mitochondrial respiratory parameters (state 2 mitochondrial respiratory activity (state 2), state 3 mitochondrial respiratory activity (state 3), respiratory control (RC), mitochondrial ATP synthetic activity (MASA), and oxidative phosphorylation efficiency (ADP:O)) were assayed in heart homogenates (HHs) and in unwashed isolated mitochondria (isolated crude heart mitochondria (CHMs)), using rats sacrificed 3, 6, 24, and 48 h after receiving a subcutaneous injection of (−)-isoproterenol (67 mg/kg body weight). With HHs, the following was observed: (a) a statistically significant activation of RC and MASA at 3 h and 6 h after drug infusion; at those times, state 2, state 3, and ADP:O were not different. (b) No studied (−)-isoproterenol mitochondrial parameters were statistically different at 24 h and 48 h after drug administration. So extrapolating, (−)-isoproterenol treatment does not negatively impact mitochondrial respiratory function in vivo; on the contrary, a better 3 h and 6 h (−)-isoproterenol mitochondrial energetic functional state was observed. With CHMs, the following was observed: (a) a statistically significant activation of RC and MASA at 3 h, but no longer at 6 h after drug infusion. (b) No studied mitochondrial parameters were statistically different at 24 h after (−)-isoproterenol treatment, but at 48 h, a statistical decrease took place in (−)-isoproterenol RC, so the mitochondrial isolation procedure (MIP) causes additional negative alterations to the mitochondrial samples; therefore, isoproterenol-induced negative alterations of mitochondrial respiratory parameters reported in the literature using isolated heart mitochondria (IHMs) are possibly an experimental artefact. Full article

Vasorelaxant and antiplatelet agents play an important role in preventing and combating endothelial dysfunction, atherosclerosis and a plethora of associated cardiovascular diseases (CVDs). CVDs are the leading cause of death worldwide and nowadays occur not only in developed but also in developing societies. They include, among others, coronary heart disease, cerebrovascular disease and peripheral artery disease. Due to their high prevalence, it is important to seek efficient preventive measures, such as lifestyle changes and the implementation of appropriate herbal dietary supplementation and treatment alternatives. Plant-derived quinones have recently drawn researchers’ attention due to their interesting biological potential. Embelin and rapanone are two plant-derived benzoquinones with anti-inflammatory and antioxidant properties. Embelin has already been shown to have vasorelaxant and antiplatelet activity, but little is known about rapanone in the context of CVDs. Therefore, we decided to comparatively evaluate their activity in a specially designed experimental protocol. Following the isolation of both benzoquinones from plant sources (rapanone from Ardisia crenata leaves; embelin from Lysimachia punctata roots), their effects were comparatively assessed in a biofunctional study on isolated rat aorta (precontracted with phenylephrine) and in vitro on platelet aggregation. Both benzoquinones showed 50% vasorelaxation in an NO-dependent manner. Interestingly, rapanone was slightly more effective as an antiplatelet agent than embelin. The antiplatelet effect of both benzoquinones was specific, as no cytotoxicity towards platelets was observed at the concentrations tested. This is the first report on the vasorelaxant and antiplatelet activity of rapanone. Full article

Background/Aim: Rosmarinus officinalis L. (R. officinalis) is an aromatic medicinal species with important nutraceutical potential, having rosmarinic acid (RA) as one of its main metabolites. The present study aims to evaluate the effects of an extract obtained from the leaves of this species and of its main metabolite in improving the streptozotocin-induced damage of hearts and aorta of diabetic rats. Methods: The leaves of the species were used to obtain a hydroethanolic extract, which was analyzed using the LC/MS method. Diabetes mellitus was induced by intraperitoneal streptozotocin administration in rats. After two weeks, oxidative stress parameters were evaluated from the heart and aorta homogenates. NOS3, AMPK, and adiponectin levels were quantified using ELISA tests, and thoracic aorta rings were isolated for contractility evaluation in the organ bath. Phospho-NF-κB, NRF2, HIF1 alfa, iNOS, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) quantification were performed using the Western blot technique. Results: Carnosic acid, together with rosmarinic acid, were proven to be the main metabolites identified in the composition of the tested extract. Administration of the extract and of RA improved the relaxation response to acetylcholine and the redox status, with the reduction in malondialdehyde (MDA), nitric oxide synthase 3 (NOS 3), AMP-activated protein kinase (AMPK), adiponectin, reduced (GSH) and oxidized glutathione (GSSG) levels, and superoxide dismutase (SOD) activity. RA significantly enhanced the expression of HIF 1α, NRF2, and pNFkB in the heart. Conclusions: Administration of the R. officinalis extract and of RA-alleviated oxidative stress, proving vascular and cardiac antioxidant properties in the hearts and aorta of diabetic rats. Full article

2′-Hydroxycinnamaldehyde (HCA), a natural product isolated from the bark of Cinnamomum cassia, has anti-inflammatory and anti-tumor activities. In this study, we explored whether HCA preconditioning could protect the heart against ischemia/reperfusion (I/R)-induced oxidative injury through cytosolic Bcl-2-associated athanogene 3 (BAG3) upregulation. In vivo HCA preconditioning was performed intraperitoneally in adult male Wistar rats (50 mg/kg body weight) three times/week for 2 weeks before cardiac I/R injury. The animals were divided into sham control (sham), I/R, and HCA preconditioning plus I/R (HCA+I/R) groups. We examined left ventricular pressure cardiac hemodynamics, the microcirculation, electrocardiograms, infarct size, and oxidative stress and performed Western blots, immunohistochemistry, and cytokine array assays. HCA pretreatment, via BAG3 overexpression, inhibited H₂O₂-induced H9c2 cell death. Cardiac I/R injury increased ST-segment elevation, left ventricular end-diastolic pressure, infarct size, myocardial disruption, tissue edema, erythrocyte accumulation, leukocyte infiltration, reactive oxygen species, malondialdehyde, 8-isoprostane, caspase 3-mediated apoptosis, 4HNE/GPX4-mediated ferroptosis, and fibrosis but decreased the microcirculation, cytosolic BAG3, and Beclin-1/LC3 II-mediated autophagy in the I/R hearts. HCA preconditioning significantly decreased these oxidative injuries by increasing cardiac cytosolic BAG3 and Nrf2/HO-1 signaling. HCA preconditioning significantly decreased cardiac I/R-enhanced mitochondrial fission DRP1 expression. Our data suggest that HCA preconditioning can efficiently improve myocardial I/R injury-induced cardiac dysfunction, apoptosis, ferroptosis, mitochondrial fission, and autophagy inhibition through cardiac BAG3 and Nrf2/HO-1 upregulation. Full article

Pterocephin A is a natural triterpenoid saponin isolated from Pterocephalus hookeri, a traditional Tibetan medicine with slight toxicity, which can induce liver injury in rats. This study aimed to establish a sensitive and reliable UPLC-MS/MS method for exploring the toxicokinetics and tissue distribution of pterocephin A following single intravenous and intragastric administration. Pterocephin A and prosapogenin 1C (internal standard, IS) were extracted using a simple protein precipitation technique with methanol as the precipitant for plasma samples and methanol/acetonitrile = 1:1 (v/v) for tissue samples. UPLC separation was achieved by gradient elution with 0.3 mL/min and a mobile phase consisting of 5 mM ammonium formate (A) and acetonitrile (B) (0–2 min 30% B; 2–4 min: 30–80% B; 4–5 min: 80–98% B; 5–6.5 min: 98% B; 6.5–7 min: 98–30% B; and 7–8 min: 30% B, v/v) with a column temperature of 35 °C. MS spectrometry adopted negative ion scanning mode, primary MS spectrometry adopted full scan monitoring mode, and secondary MS spectrometry adopted targeted MS2 scan monitoring mode. The assay exhibited a linear dynamic range of 0.02–15 μg/mL for pterocephin A in biological samples, with the low limit of quantification set at 0.02 μg/mL. Non-compartmental toxicokinetic parameters indicated that pterocephin A was well absorbed into the systemic circulation and had a long residual time after intravenous (10 mg/kg) and intragastric (60 mg/kg) administration, as it could still be detected after 72 h. Tissue distribution analysis revealed detectable levels of pterocephin A in various tissues, and a high concentration was maintained in the liver after intravenous (10 mg/kg) administration, with the highest concentration being 610.95 ± 25.73 ng/mL and a specific distribution pattern of liver > lung > kidney > intestine > spleen > testes > heart > stomach. The toxicokinetic process and tissue distribution characteristics of pterocephin A were expounded in this study, which can provide relevant data support for further research and clinical application of pterocephin A with its slight toxicity. Full article

Intolerance to exercise is a symptom associated with chronic heart failure (CHF) resulting in SM waste and weakness in humans. The effect of CHF on skeletal muscle (SM) arose from experimental evidence in rat models to explain the underlying mechanism. We investigated SM mechanical and metabolic properties in sham rats and with coronary ligation-induced CHF. After twelve weeks of CHF, rats were catheterized to measure right auricular pressure, SM mechanical properties, SERCA-ATPase activity and plasma membrane Ca²⁺-ATPase (PMCA) hydrolytic activity in isolated sarcoplasmic reticulum (SR) and transverse tubule (TT membrane), respectively, in the sham and CHF. The right auricular pressure and plasma nitrite concentration in CHF increased two-fold with respect to the sham. Pleural effusion and ascites were detected in CHF, confirming CHF. SERCA activity was conserved in CHF. In TT membranes from CHF, the glucose transporter GLUT4 increased seven-fold, and the PMCA hydrolytic activity increased five-fold, but in isolated muscle, the mechanical properties were unaffected. The absence of a deleterious effect of coronary ligation-induced CHF in the rat model on SM could be explained by the increased activity of PMCA and increased presence of GLUT-4 on the TT membrane, which may be involved in the mechanical outcome of the EDL. Full article