Elucidation of The Effects and Underlying Mechanism of Aerobic Interval Training Combined With Liraglutide On Diabetic Cardiomyopathy

objective: This study intended to explore the hypoglycemic and cardioprotective effects of 8-week aerobic interval training combined with liraglutide and elucidate the underlying mechanisms.Method: Male Wistar rats were randomly divided into 5 groups - normal control (CON), diabetic cardiomyopathy (DCM), high-dose liraglutide (DH), low-dose liraglutide DL , and aerobic interval training combined with liraglutide (DLE). The cardiac function of rats ,the FBG the levels of fasting insulin (FIN), HbA1c, the total collagen content , AGEs, the mRNA expression of myocardial remodeling genes BNP, GSK3β, α-MHC, and β-MHC ,the expression of GLP-1 and GLP-1R proteins, Insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) was analyze. Results: During the intervention, the FBG in each intervention group significantly decreased compared to the DCM group. After 8 weeks,the DH, DL, and DLE groups showed improved blood glucose-related indices and cleared the accumulated AGEs in the DCM groups. The heart function in the DLE groups was significantly improved than that in the DH and DL groups. The relative expression of BNP mRNA in the DH, DL, and DLE groups significantly reduced compared to the CON and the DCM group .Compared to the DCM group,the relative expression of α-MHC mRNA increased significantly and β-MHC mRNA decreased notably in the myocardium of the DH, DL, and the DLE group.The expression of GLP-1 in the myocardial tissue of rats in the DH group was higher than that in the DL and DLE groups. GLP-1R expression in the myocardial tissue in the DLE group was higher than that in the DH , DL and the DCM groups .Conclusion: Liraglutide combined with AIT intervention significantly reduced FBG and the fluctuations in FBG, alleviated myocardial fibrosis, improved cardiac function in DCM rats, supporting the efficacy of the combined pharmaceutical and physical intervention, and reduced the cost of treatment.

The Diagnostic and Therapeutic Potential of Galectin-3 in Cardiovascular Diseases

Galectin-3 plays a prominent role in chronic inflammation and has been implicated in the development of many disease conditions, including heart disease. Galectin-3, a regulatory protein, is elevated in both acute and chronic heart failure and is involved in the inflammatory pathway after injury leading to myocardial tissue remodelling. We discussed the potential utility of galectin-3 as a diagnostic and disease severity/prognostic biomarker in different cardio/cerebrovascular diseases, such as acute ischemic stroke, acute coronary syndromes, heart failure and arrhythmogenic cardiomyopathy. Over the last decade there has been a marked increase in the understanding the role of galectin-3 in myocardial fibrosis and inflammation and as a therapeutic target for the treatment of heart failure and myocardial infarction.

Sequential Coupling Shows Minor Effects of Fluid Dynamics on Myocardial Deformation in a Realistic Whole-Heart Model

Background: The human heart is a masterpiece of the highest complexity coordinating multi-physics aspects on a multi-scale range. Thus, modeling the cardiac function in silico to reproduce physiological characteristics and diseases remains challenging. Especially the complex simulation of the blood's hemodynamics and its interaction with the myocardial tissue requires a high accuracy of the underlying computational models and solvers. These demanding aspects make whole-heart fully-coupled simulations computationally highly expensive and call for simpler but still accurate models. While the mechanical deformation during the heart cycle drives the blood flow, less is known about the feedback of the blood flow onto the myocardial tissue.Methods and Results: To solve the fluid-structure interaction problem, we suggest a cycle-to-cycle coupling of the structural deformation and the fluid dynamics. In a first step, the displacement of the endocardial wall in the mechanical simulation serves as a unidirectional boundary condition for the fluid simulation. After a complete heart cycle of fluid simulation, a spatially resolved pressure factor (PF) is extracted and returned to the next iteration of the solid mechanical simulation, closing the loop of the iterative coupling procedure. All simulations were performed on an individualized whole heart geometry. The effect of the sequential coupling was assessed by global measures such as the change in deformation and—as an example of diagnostically relevant information—the particle residence time. The mechanical displacement was up to 2 mm after the first iteration. In the second iteration, the deviation was in the sub-millimeter range, implying that already one iteration of the proposed cycle-to-cycle coupling is sufficient to converge to a coupled limit cycle.Conclusion: Cycle-to-cycle coupling between cardiac mechanics and fluid dynamics can be a promising approach to account for fluid-structure interaction with low computational effort. In an individualized healthy whole-heart model, one iteration sufficed to obtain converged and physiologically plausible results.

Acute Heart Failure After Reperfused Ischemic Stroke: Association With Systemic and Cardiac Inflammatory Responses

Patients with acute ischemic stroke (AIS) present an increased incidence of systemic inflammatory response syndrome and release of Troponin T coinciding with cardiac dysfunction. The nature of the cardiocirculatory alterations remains obscure as models to investigate systemic interferences of the brain-heart-axis following AIS are sparse. Thus, this study aims to investigate acute cardiocirculatory dysfunction and myocardial injury in mice after reperfused AIS. Ischemic stroke was induced in mice by transient right-sided middle cerebral artery occlusion (tMCAO). Cardiac effects were investigated by electrocardiograms, 3D-echocardiography, magnetic resonance imaging (MRI), invasive conductance catheter measurements, histology, flow-cytometry, and determination of high-sensitive Troponin T (hsTnT). Systemic hemodynamics were recorded and catecholamines and inflammatory markers in circulating blood and myocardial tissue were determined by immuno-assay and flow-cytometry. Twenty-four hours following tMCAO hsTnT was elevated 4-fold compared to controls and predicted long-term survival. In parallel, systolic left ventricular dysfunction occurred with impaired global longitudinal strain, lower blood pressure, reduced stroke volume, and severe bradycardia leading to reduced cardiac output. This was accompanied by a systemic inflammatory response characterized by granulocytosis, lymphopenia, and increased levels of serum-amyloid P and interleukin-6. Within myocardial tissue, MRI relaxometry indicated expansion of extracellular space, most likely due to inflammatory edema and a reduced fluid volume. Accordingly, we found an increased abundance of granulocytes, apoptotic cells, and upregulation of pro-inflammatory cytokines within myocardial tissue following tMCAO. Therefore, reperfused ischemic stroke leads to specific cardiocirculatory alterations that are characterized by acute heart failure with reduced stroke volume, bradycardia, and changes in cardiac tissue and accompanied by systemic and local inflammatory responses.

mTOR inhibitor improves testosterone-induced myocardial hypertrophy in hypertensive rats

Compelling evidence have described the incidence of hypertension and left ventricular hypertrophy (LVH) in postmenopausal women is significantly increased worldwide. Our team’s previous research identified that androgen was an underlying factor contributing to increased blood pressure and LVH in postmenopausal women. However, little is known about how androgens affect LVH in postmenopausal hypertensive women. The purpose of this study was to evaluate the role of mTOR signaling pathway in myocardial hypertrophy in androgen-induced postmenopausal hypertension and whether mTOR inhibitors can protect the myocardium from androgen-induced interference to prevent and treat cardiac hypertrophy. For that, ovariectomized (OVX) spontaneously hypertensive rats (SHR) aged 12 weeks were used to study the effects of testosterone (T 2.85 mg/kg/weekly im) on blood pressure and myocardial tissue. On the basis of antihypertensive therapy (chlorthalidone 8mg/kg/day ig), the improvement of blood pressure and myocardial hypertrophy in rats treated with different dose gradients of rapamycin (0.8mg/kg/day Vs 1.5mg/kg/day Vs 2mg/kg/day ip) in OVX+ estrogens(E 9.6 mg/Kg/day, ig)+T group was further evaluated. After T intervention, the OVX female rats exhibited significant increments in the heart weight / tibial length (TL), area of cardiomyocytes and the mRNA expressions of atrial natriuretic peptide, β- myosin heavy chain and matrix metalloproteinase 9 accompanied by a significant reduction in the uterine weight/TL and issue inhibitor of metalloproteinase 1. Mammalian rapamycin receptor (mTOR), ribosomal protein S6 kinase (S6K1),4E-bindiong protein 1(4EBP1) and eukaryotic translation initiation factor 4E in myocardial tissue of OVX+E+T group were expressed at higher levels than those of the other four groups. On the other hand, rapamycin abolished the effects of T-induced cardiac hypertrophy, decreased the systolic and diastolic blood pressure of SHR, and inhibited the activation of mTOR/ S6K1/4EBP1 signaling pathway in a concentration-dependent manner. Collectively, these data suggest that the mTOR/S6K1/4EBP1 pathway is an important therapeutic target for the prevention of LVH in postmenopausal hypertensive female rats with high T levels. Our findings also support the standpoint that the mTOR inhibitor, rapamycin, can eliminate T-induced cardiomyocyte hypertrophy

Proteomic mapping of atrial and ventricular heart tissue in patients with aortic valve stenosis

Aortic valve stenosis (AVS) is one of the most common valve diseases in the world. However, detailed biological understanding of the myocardial changes in AVS hearts on the proteome level is still lacking. Proteomic studies using high-resolution mass spectrometry of formalin-fixed and paraffin-embedded (FFPE) human myocardial tissue of AVS-patients are very rare due to methodical issues. To overcome these issues this study used high resolution mass spectrometry in combination with a stem cell-derived cardiac specific protein quantification-standard to profile the proteomes of 17 atrial and 29 left ventricular myocardial FFPE human myocardial tissue samples from AVS-patients. In our proteomic analysis we quantified a median of 1980 (range 1495–2281) proteins in every single sample and identified significant upregulation of 239 proteins in atrial and 54 proteins in ventricular myocardium. We compared the proteins with published data. Well studied proteins reflect disease-related changes in AVS, such as cardiac hypertrophy, development of fibrosis, impairment of mitochondria and downregulated blood supply. In summary, we provide both a workflow for quantitative proteomics of human FFPE heart tissue and a comprehensive proteomic resource for AVS induced changes in the human myocardium.