25 research outputs found
Proteomic analysis of exercise-induced hypertrophy reveals sexrelated mitochondrial differences mediated by AMPK : [abstract]
Comparison of speckle-tracking echocardiography with invasive hemodynamics for the detection of characteristic cardiac dysfunction in type-1 and type-2 diabetic rat models
BACKGROUND: Measurement of systolic and diastolic function in animal models is challenging by conventional non-invasive methods. Therefore, we aimed at comparing speckle-tracking echocardiography (STE)-derived parameters to the indices of left ventricular (LV) pressure-volume (PV) analysis to detect cardiac dysfunction in rat models of type-1 (T1DM) and type-2 (T2DM) diabetes mellitus. METHODS: Rat models of T1DM (induced by 60 mg/kg streptozotocin, n = 8) and T2DM (32-week-old Zucker Diabetic Fatty rats, n = 7) and corresponding control animals (n = 5 and n = 8, respectively) were compared. Echocardiography and LV PV analysis were performed. LV short-axis recordings were used for STE analysis. Global circumferential strain, peak strain rate values in systole (SrS), isovolumic relaxation (SrIVR) and early diastole (SrE) were measured. LV contractility, active relaxation and stiffness were measured by PV analysis. RESULTS: In T1DM, contractility and active relaxation were deteriorated to a greater extent compared to T2DM. In contrast, diastolic stiffness was impaired in T2DM. Correspondingly, STE described more severe systolic dysfunction in T1DM. Among diastolic STE parameters, SrIVR was more decreased in T1DM, however, SrE was more reduced in T2DM. In T1DM, SrS correlated with contractility, SrIVR with active relaxation, while in T2DM SrE was related to cardiac stiffness, cardiomyocyte diameter and fibrosis. CONCLUSIONS: Strain and strain rate parameters can be valuable and feasible measures to describe the dynamic changes in contractility, active relaxation and LV stiffness in animal models of T1DM and T2DM. STE corresponds to PV analysis and also correlates with markers of histological myocardial remodeling
A hipertrófiás myocardium reverz elektromos remodellációjának vizsgálata patkánymodellben = Reverse electrical remodeling following pressure unloading in a rat model of myocardial hypertrophy
A szolubilis guanilát-cikláz aktivátor cinaciguat megelőzi a kardiális diszfunkció kialakulását 1-es típusú cukorbetegség patkánymodelljében = The soluble guanylate cyclase activator cinaciguat prevents cardiac dysfunction in a rat model of type-1 diabetes mellitus
Myofilament Ca2+ sensitivity correlates with left ventricular contractility during the progression of pressure overload-induced left ventricular myocardial hypertrophy in rats
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Balanced Intense Exercise Training Induces Atrial Oxidative Stress Counterbalanced by the Antioxidant System and Atrial Hypertrophy That Is Not Associated with Pathological Remodeling or Arrhythmogenicity
Although regular exercise training is associated with cardiovascular benefits, the increased risk of atrial arrhythmias has been observed after vigorous exercise and has been related to oxidative stress. We aimed at investigating exercise-induced atrial remodeling in a rat model of an athlete's heart and determining sex-specific differences. Age-matched young adult rats were divided into female exercised, female control, male exercised, and male control groups. After exercised animals completed a 12-week-long swim training protocol, echocardiography and in vivo cardiac electrophysiologic investigation were performed. Additionally, atrial histological and gene expression analyses were carried out. Post-mortem atrial weight data and histological examination confirmed marked atrial hypertrophy. We found increased atrial gene expression of antioxidant enzymes along with increased nitro-oxidative stress. No gene expression alteration was found regarding markers of pathological remodeling, apoptotic, proinflammatoric, and profibrotic processes. Exercise training was associated with a prolonged right atrial effective refractory period. We could not induce arrhythmias by programmed stimulation in any groups. We found decreased expression of potassium channels. Female gender was associated with lower profibrotic expression and collagen density. Long-term, balanced exercise training-induced atrial hypertrophy is not associated with harmful electrical remodeling, and no inflammatory or profibrotic response was observed in the atrium of exercised rats
Long-Term PDE-5A Inhibition Improves Myofilament Function in Left and Right Ventricular Cardiomyocytes through Partially Different Mechanisms in Diabetic Rat Hearts
Heart failure with preserved ejection fraction (HFpEF) and right ventricular (RV) dysfunc-
tion are frequent complications of diabetic cardiomyopathy. Here we aimed to characterize RV and
left ventricular (LV) remodeling and its prevention by vardenafil (a long-acting phosphodiesterase-
5A (PDE-5A) inhibitor) administration in a diabetic HFpEF model. Zucker Diabetic Fatty (ZDF)
and control, ZDF Lean (Lean) male rats received 10 mg/kg vardenafil (ZDF + Vard; Lean + Vard)
per os, on a daily basis for a period of 25 weeks. In vitro force measurements, biochemical and
histochemical assays were employed to assess cardiomyocyte function and signaling. Vardenafil
treatment increased cyclic guanosine monophosphate (cGMP) levels and decreased 3-nitrotyrosine
(3-NT) levels in the left and right ventricles of ZDF animals, but not in Lean animals. Cardiomyocyte
passive tension (Fpassive) was higher in LV and RV cardiomyocytes of ZDF rats than in those receiving
preventive vardenafil treatment. Levels of overall titin phosphorylation did not differ in the four
experimental groups. Maximal Ca2+-activated force (Fmax) of LV and RV cardiomyocytes were
preserved in ZDF animals. Ca2+-sensitivity of isometric force production (pCa50) was significantly
higher in LV (but not in RV) cardiomyocytes of ZDF rats than in their counterparts in the Lean or Lean
+ Vard groups. In accordance, the phosphorylation levels of cardiac troponin I (cTnI) and myosin
binding protein-C (cMyBP-C) were lower in LV (but not in RV) cardiomyocytes of ZDF animals than
in their counterparts of the Lean or Lean + Vard groups. Vardenafil treatment normalized pCa50
values in LV cardiomyocytes, and it decreased pCa50 below control levels in RV cardiomyocytes in
the ZDF + Vard group. Our data illustrate partially overlapping myofilament protein alterations
for LV and RV cardiomyocytes in diabetic rat hearts upon long-term PDE-5A inhibition. While
uniform patterns in cGMP, 3-NT and Fpassive levels predict identical effects of vardenafil therapy
for the diastolic function in both ventricles, the uneven cTnI, cMyBP-C phosphorylation levels and
pCa50 values implicate different responses for the systolic function
Sex-related differences of early cardiac functional and proteomic alterations in a rat model of myocardial ischemia
A miofilamentáris rendszer Ca2+-érzékenysége korrellál a bal kamrai kontraktilitással a fokozott nyomásterhelés által előidézett patológiás szívizom-hipertrófia patkánymodelljében
Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapy
DNA transposon-based gene delivery vectors represent a promising new branch of randomly integrating vector development
for gene therapy. For the side-by-side evaluation of the
piggyBac and Sleeping Beauty systems—the only DNA transposons currently employed in clinical trials—during therapeutic
intervention, we treated the mouse model of tyrosinemia type
I with liver-targeted gene delivery using both transposon vectors. For genome-wide mapping of transposon insertion sites
we developed a new next-generation sequencing procedure
called streptavidin-based enrichment sequencing, which allowed
us to identify approximately one million integration sites for
both systems. We revealed that a high proportion of piggyBac
integrations are clustered in hot regions and found that they
are frequently recurring at the same genomic positions among
treated animals, indicating that the genome-wide distribution
of Sleeping Beauty-generated integrations is closer to random.
We also revealed that the piggyBac transposase protein exhibits
prolonged activity, which predicts the risk of oncogenesis by
generating chromosomal double-strand breaks. Safety concerns
associated with prolonged transpositional activity draw attention to the importance of squeezing the active state of the transposase enzymes into a narrower time window