The effects of exercise training on cardiac matrix metalloproteinases activity and cardiac function in mice with diabetic cardiomyopathy

Dede, Eleni; Liapis, D.; Davos, Constantinos H.; Katsimpoulas, Michalis; Varela, Aimilia; Mpotis, Ioannis; Kostomitsopoulos, Nikolaos; Kadoglou, Nikolaos P.E.

doi:10.1016/j.bbrc.2021.11.013

Cited by 12 publications

(8 citation statements)

References 35 publications

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“…We believe that the findings of reduced LV longitudinal strain and mitral annular displacement in patients with T2D by aCMQ and TMAD suggested early myocardial damage in patients with diabetes, and clinicians should be informed to commence early intervention to ameliorate and stop the progression of diabetic cardiomyopathy. Many researchers have noted that exercise could help prevent cardiomyocyte apoptosis, myocardial fibrosis, and oxidative stress, which could moderately delay the development of diabetic myocardial damage [33][34][35] .…”

Section: Discussionmentioning

confidence: 99%

Feasibility study of automated cardiac motion quantification to assess left ventricular function in type 2 diabetes

2023

Sci Rep

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The global incidence of diabetes and related complications is gradually increasing, with cardiovascular complications being the leading cause of death in the diabetic population. The purpose of this study was to examine left ventricular function in individuals with type 2 diabetes mellitus (T2D) and conduct a feasibility analysis using automated cardiac motion quantification (aCMQ) approach. A total of 150 T2D patients with a history of diabetes mellitus dating back more than 10 years were chosen, and we treated 87 patients with T2D that had been present for less than 15 years as group I, 63 patients with T2D that had been present for more than 15 years as group II, and 50 healthy volunteers as the control group. From the three groups, clinical information, conventional ultrasonography parameters, and mitral annular plane systolic excursion (MAPSE) parameters were gathered. aCMQ technique was used to collect longitudinal strain and circumferential strain in the left ventricle. Tissue motion mitral annular displacement technique (TMAD) in aCMQ was used to collect parameters related to TMAD, and cardiac motion quantification (CMQ) was used to collect two-dimensional global longitudinal strain (2D-GLS) to compare the degree of difference between the aforementioned three groups. The differences between longitudinal strain groups in aCMQ were all statistically significant and gradually decreased with increasing disease duration. Most TMAD parameters were lower in groups I and II than in the control group, and TMAD parameters gradually decreased with increasing disease duration. The results of the LV global longitudinal strain and 2D-GLS using Bland–Altman analyses showed high agreement between and within groups, Pearson correlation analysis showed a significant positive correlation (r = 0.18, P < 0.05), and the AUC of ROC curves predicting the value of left ventricular function in patients with T2D was 0.723 and 0.628, respectively. With significant positive correlations between MAPSE, s', and the majority of the TAMD parameters (P < 0.05), TAMD, MAPSE, and s' demonstrated high inter- and intra-group agreement using Bland–Altman analyses, and the three had predictive value in assessing left ventricular function in T2D patients by ROC curve. Reduced longitudinal strain and reduced mitral annular displacement were seen in patients with different disease stages of T2D, so the application of aCMQ and TAMD was effective in detecting altered left ventricular function in patients with T2D. aCMQ had higher value in predicting left ventricular function in patients with T2D compared to CMQ for overall longitudinal strain, and the software performed the depiction automatically, reducing manual errors. MAPSE parameters and s ' can replace the TMAD technique for assessing mitral annular motion and was simpler to perform, saving operational time.

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Section: Discussionmentioning

confidence: 99%

Feasibility study of automated cardiac motion quantification to assess left ventricular function in type 2 diabetes

2023

Sci Rep

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“…Management of diabetic cardiomyopathy and cardiac hypertrophic patients should not only simply focus on normalization of blood glucose and pressure, but also have to target the adverse structural and functional feature that cause ventricular remodeling including CVM and non-CVM compartments by diabetes (20, 32, 42). The integrin ligands might be the potential drug candidates for the treatment and/or prevention of human diseases including diabetes and cardiovascular diseases (7, 19, 22, 37, 87, 96, 99). Thus, understanding the mechanisms that integrin modulated biomechanical forces to the activation of stress pathways will give insight into the biology of heart diseases.…”

Section: Discussionmentioning

confidence: 99%

Fibronectin improves the impaired calcium signaling and myofilament activation in diabetic cardiomyocytes

Trzeciakowski

Meininger

et al. 2022

Preprint

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Ventricular remodeling is one of the primary adaptive mechanisms in response to long-term mechanical overload in diabetes. In addition to cardiomyocyte hypertrophy, alterations in non-cardiomyocyte compartments [e.g. extracellular matrix (ECM)] are an essential process in the remodeling of ventricle during diabetes. Integrins that link the ECM and intracellular cytoskeleton function as mechanotransducers to translate the mechanical force to intracellular signals. We hypothesize that mechanotransduction mechanisms are altered in diabetic cardiomyopathy mouse hearts. To test this hypothesis, force and intracellular calcium ([Ca2+]i) measurements on papillary muscle fibers were investigated in adult mouse cardiomyocytes from normal (non-db) and type 2 diabetic (db/db) mice. In addition, atomic force microscopy (AFM) was used to measure adhesion force between integrin receptors and ECM protein fibronectin (FN) by quantifying the unbinding force required to break FN-cardiomyocytes (integrin) bonds. In db/db mice, the peak active force decreased at 71% or 73% while the peak of [Ca2+]i decreased at 64% and 68% at 1 Hz or 2 Hz. In the presence of the FN (35 nM), active force was increased significantly by 40-50% in db/db mice. Furthermore, increased active force in the presence of FN was associated with 26-42% increase in [Ca2+]i at all giving stimulations of 1 Hz and 2 Hz in db/db mice, respectively. The increased effects on force and [Ca2+]i caused by FN were greater in ventricular muscles from db/db mice than from non-db mice. The unbinding force between FN (2.7 mM) coated AFM probes and cardiomyocyte in db/db was 52% higher than non-db (58.3 pN vs 38.6 pN. p < 0.05). The binding probability of FN-cardiomyocytes, calculated as number of force curves with adhesion / number of total force curves sampled, was significantly reduced by 30% in db/db cardiomyocytes when compared to normal. In addition, the cell stiffness, representing changes in Ca2+ signaling and cytoskeletal reorganization, was 19% increase in db/db cardiomyocytes. The presented data indicate that dynamic changes of the mechanical properties of integrin-ECM interactions may contribute to impaired intracellular Ca2+ signaling and myofilament activation in the diabetic cardiomyopathy.

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“…After STZ injections, mice maintaining fasting glucose levels >200 mg/dL were considered diabetic and were included in the study analysis. This is a valid animal model for diabetic atherosclerosis development which we have previously used in pharmaceutical studies [48,49]. After diabetes induction (8th week of experiment), mice continued HFD and were randomized into the following four groups (n=12) for the last 6 weeks of the study period:…”

Section: Animal Model and Experimental Designmentioning

confidence: 99%

The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study

Stasinopoulou,

Kostomitsopoulos,

Kadoglou

2024

Preprint

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Bosentan, an endothelin-receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male apoE-/- mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin and mice were randomized into 4 groups: 1) Control/COG: no intervention. 2) ΒΟG: bosentan 100 mg/kg/day per os. 3) ATG: atorvastatin 20mg/kg/day per os). 4) BO+ATG: Combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix-metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentrations were determined. The percentage of lumen stenosis significantly decreased across all treated groups: BOG: 19.5±2.2%, ATG: 12.8±4.8%, BO+ATG: 9.1±2.7% compared to controls (24.6±4.8%, p&lt;0.001). Both atorvastatin and bosentan significantly increased collagen content and fibrous cap thickness versus COG (p&lt;0.01). All intervention groups reduced the relative intra-plaque concentrations of MCP-1, MMP-3,-9, and increased TIMP-1 compared to COG (p&lt;0.001). Importantly, bosentan showed modest but additive to atorvastatin effects on the latter parameters compared COG (p&lt;0.05). Bosentan treatment in diabetic, atherosclerotic apoE-/- mice delayed the atherosclerosis progression and enhanced plaques’ stability, showing modest but complementary effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.

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The effects of exercise training on cardiac matrix metalloproteinases activity and cardiac function in mice with diabetic cardiomyopathy

Cited by 12 publications

References 35 publications

Feasibility study of automated cardiac motion quantification to assess left ventricular function in type 2 diabetes

Feasibility study of automated cardiac motion quantification to assess left ventricular function in type 2 diabetes

Fibronectin improves the impaired calcium signaling and myofilament activation in diabetic cardiomyocytes

The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study

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