Effects of Endurance Training on Detrimental Structural, Cellular, and Functional Alterations in Skeletal Muscles of Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is underpinned by detrimental skeletal muscle alterations that contribute to disease severity, yet underlying mechanisms and therapeutic treatments remain poorly established. This study used a nonhuman animal model of HFpEF to better understand whether skeletal muscle abnormalities were (1) fiber-type specific and (2) reversible by various exercise training regimes.

Methods And Results: Lean control rats were compared with obese ZSF1 rats at 20 weeks and then 8 weeks after sedentary, high-intensity interval training, or moderate continuous treadmill exercise.

Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity-Driven Heart Failure With a Preserved Ejection Fraction.

Background: Respiratory muscle weakness contributes to exercise intolerance in patients with heart failure with a preserved ejection fraction (HFpEF)-a condition characterized by multiple comorbidities with few proven treatments. We aimed, therefore, to provide novel insight into the underlying diaphragmatic alterations that occur in HFpEF by using an obese cardiometabolic rat model and further assessed whether exercise training performed only after the development of overt HFpEF could reverse impairments.

Methods And Results: Obese ZSF1 rats (n=12) were compared with their lean controls (n=8) at 20 weeks, with 3 additional groups of obese ZSF1 rats compared at 28 weeks following 8 weeks of either sedentary behavior (n=13), high-intensity interval training (n=11), or moderate-continuous training (n=11).

Circulating microRNAs predict future fatal myocardial infarction in healthy individuals - The HUNT study.

Coronary heart disease is the most common cause of death, and the number of individuals at risk is increasing. To better manage this pandemic, improved tool for risk prediction, including more accurate biomarkers are needed. The objective of this study was to assess the utility of circulating microRNAs (miRs) to predict future fatal acute myocardial infarction (AMI) in healthy participants.

Cardiac LXRα protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization.

Pathological cardiac hypertrophy is characterized by a shift in metabolic substrate utilization from fatty acids to glucose, but the molecular events underlying the metabolic remodeling remain poorly understood. Here, we investigated the role of liver X receptors (LXRs), which are key regulators of glucose and lipid metabolism, in cardiac hypertrophic pathogenesis. Using a transgenic approach in mice, we show that overexpression of LXRα acts to protect the heart against hypertrophy, fibrosis, and dysfunction.

Heart failure with preserved ejection fraction induces molecular, mitochondrial, histological, and functional alterations in rat respiratory and limb skeletal muscle.

Aims: Peripheral muscle dysfunction is a key mechanism contributing to exercise intolerance (i.e. breathlessness and fatigue) in heart failure patients with preserved ejection fraction (HFpEF); however, the underlying molecular and cellular mechanisms remain unknown.

Reversible pulmonary trunk banding: IX. G6PD activity of adult goat myocardium submitted to ventricular retraining.

Objective: Increased glucose 6-phosphate dehydrogenase activity has been demonstrated in heart failure. This study sought to assess myocardial glucose 6-phosphate dehydrogenase activity in retraining of the subpulmonary ventricle of adult goats.

Methods: Eighteen adult goats were divided into three groups: traditional (fixed banding), sham, and intermittent (adjustable banding, daily 12-hour systolic overload).

Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure.

Although aberrant reactivation of embryonic gene programs is intricately linked to pathological heart disease, the transcription factors driving these gene programs remain ill-defined. Here we report that increased calcineurin/Nfat signalling and decreased miR-25 expression integrate to re-express the basic helix-loop-helix (bHLH) transcription factor dHAND (also known as Hand2) in the diseased human and mouse myocardium. In line, mutant mice overexpressing Hand2 in otherwise healthy heart muscle cells developed a phenotype of pathological hypertrophy.

A deep sequencing approach to uncover the miRNOME in the human heart.

MicroRNAs (miRNAs) are a class of non-coding RNAs of ∼22 nucleotides in length, and constitute a novel class of gene regulators by imperfect base-pairing to the 3'UTR of protein encoding messenger RNAs. Growing evidence indicates that miRNAs are implicated in several pathological processes in myocardial disease. The past years, we have witnessed several profiling attempts using high-density oligonucleotide array-based approaches to identify the complete miRNA content (miRNOME) in the healthy and diseased mammalian heart.

Reversible pulmonary trunk banding VIII: Intermittent overload causes harmless hypertrophy in adult goat.

Background: Traditional pulmonary artery banding (PAB) is not always suitable for mature subpulmonary ventricle retraining. We sought to assess in detail the myocardial morphologic adaptations of two different protocols for inducing right ventricular (RV) hypertrophy in an adult animal model.

Methods: Eighteen adult goats were distributed into three groups: sham (no systolic overload), traditional (continuous systolic overload), and intermittent (daily 12-hour systolic overload).

Reversible pulmonary trunk banding: VII. Stress echocardiographic assessment of rapid ventricular hypertrophy in young goats.

Background: Ventricle retraining with abrupt systolic overload can cause myocardial edema and necrosis, followed by late ventricular failure. Intermittent systolic overload could minimize the inadequacy of conventional pulmonary artery banding. The present study compared ventricle function under dobutamine stress in 2 protocols of systolic overload in young goats.

Reversible pulmonary trunk banding. VI: Glucose-6-phosphate dehydrogenase activity in rapid ventricular hypertrophy in young goats.

Objective: Increased myocardial glucose-6-phosphate dehydrogenase (G6PD) activity occurs in heart failure. This study compared G6PD activity in 2 protocols of right ventricle (RV) systolic overload in young goats.

Methods: Twenty-seven goats were separated into 3 groups: sham (no overload), continuous (continuous systolic overload), and intermittent (four 12-hour periods of systolic overload paired with a 12-hour resting period).

Intermittent systolic overload promotes better myocardial performance in adult animals.

Background: Corrected transposition of great arteries often evolves with right ventricular dysfunction. The ventricular preparation for anatomic correction in adult patients has produced disappointing results.

Objective: To assess right ventricular hypertrophy (RV) induced by conventional and intermittent pulmonary banding (PB) in adult animals.

Ace gene dosage influences the development of renovascular hypertension.

1. Clinical and experimental evidence highlights the importance of the renin-angiotensin system in renovascular hypertension. Furthermore, genetic factors affecting angiotensin-converting enzyme (ACE) could influence the development of renovascular hypertension.

Association between glutathione S-transferase polymorphisms and triglycerides and HDL-cholesterol.

Objective: Null genotypes of glutathione S-transferase (GSTs) exhibit absence of enzymatic activity and are hypothesized to modulate an increased risk of developing cardiovascular disease. The aim of this study was to identify the potential association between GSTM1 and GSTT1 deleted polymorphisms with cardiovascular risk factors and coronary atherosclerosis in two independent urban populations.

Methods And Results: Genotype distribution of GSTM1 and GSTT1 deleted polymorphism were examined in a sample of 1577 individuals from the general population and a replication sample of 871 individuals submitted to coronary angiography.

Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice.

We tested the hypothesis that small changes in angiotensin I-converting enzyme (ACE) expression can alter the vascular response to injury. Male mice containing one, two, three, and four copies of the Ace gene with no detectable vascular abnormality or changes in blood pressure were submitted to cuff-induced femoral artery injury. Femoral thickening was higher in 3- and 4-copy mice (42.

Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR.

To dissect the genetic architecture controlling blood pressure (BP) regulation in the spontaneously hypertensive rat (SHR) we derived congenic rat strains for four previously mapped BP quantitative trait loci (QTLs) in chromosomes 2, 4, and 16. Target chromosomal regions from the Brown Norway rat (BN) averaging 13-29 cM were introgressed by marker-assisted breeding onto the SHR genome in 12 or 13 generations. Under normal salt intake, QTLs on chromosomes 2a, 2c, and 4 were associated with significant changes in systolic BP (13, 20, and 15 mmHg, respectively), whereas the QTL on chromosome 16 had no measurable effect.

[IV Pulmonary trunk reversible banding: analysis of right ventricle acute hypertrophy in an intermittent loading experimental model].

Objectives: Adjustable pulmonary trunk (PT) banding device may induce a more physiologic ventricle retraining for the two-stage Jatene operation. This experimental study evaluates the acute hypertrophy (96 hours) of the right ventricle (RV) submitted to an intermittent pressure overload.

Methods: Five groups of seven young goats were distributed according to RV intermittent systolic overload duration (0, 24, 48, 72 and 96 hours).

Effects of sinoaortic denervation on hemodynamic parameters during natural sleep in rats.

Study Objectives: To analyze the role of arterial baroreflex on hemodynamic changes during synchronized and desynchronized sleep phases of natural sleep in rats.

Design: Experimental study.

Setting: Laboratory.

Genetic mapping of a new heart rate QTL on chromosome 8 of spontaneously hypertensive rats.

Background: Tachycardia is commonly observed in hypertensive patients, predominantly mediated by regulatory mechanisms integrated within the autonomic nervous system. The genetic loci and genes associated with increased heart rate in hypertension, however, have not yet been identified.

Methods: An F2 intercross of Spontaneously Hypertensive Rats (SHR) x Brown Norway (BN) linkage analysis of quantitative trait loci mapping was utilized to identify candidate genes associated with an increased heart rate in arterial hypertension.

ACE gene dosage modulates pressure-induced cardiac hypertrophy in mice and men.

The influence of genetic factors on complex phenotypes is context dependent, posing a challenge to quantify the role of single gene variants on this process. Moreover, redundancy and reserve capacity among control systems prevent most physiological stimuli to destabilize these processes. To test whether small gene perturbation can disrupt this equilibrium under pathological conditions, mice harboring one, two, or three copies of the angiotensin converting enzyme (Ace) gene were submitted to 3 and 6 wk of pressure overload (PO).

Resetting of aortic baroreceptors in response to hypotension does not alter gain sensitivity.

1. In chronic hypertension, the baroreceptors reset to hypertensive levels with a decrease in gain sensitivity, but only a few studies have evaluated baroreceptor resetting during chronic hypotension and, under these conditions, no consistent information is available concerning changes in baroreceptor gain sensitivity. Therefore, in the present study, the aortic baroreceptor function curve and the baroreflex control of heart rate (HR) were evaluated in chronic hypotension produced by myocardial infarction (MI) with no heart failure.

Exercise training improves aortic depressor nerve sensitivity in rats with ischemia-induced heart failure.

Exercise training improves arterial baroreflex control in heart failure (HF) rabbits. However, the mechanisms involved in the amelioration of baroreflex control are unknown. We tested the hypothesis that exercise training would increase the afferent aortic depressor nerve activity (AODN) sensitivity in ischemic-induced HF rats.

Skeletal muscle cells expressing VEGF induce capillary formation and reduce cardiac injury in rats.

Background: We tested a preemptive combined cell/gene therapy strategy of skeletal myoblasts transfected with Ad(5)RSVVEGF-165 in an ischemia/reperfusion rat model to increase collateral blood flow to nonischemic heart tissue.

Methods: Lewis rats were injected with placebo (Control), 10(6) skeletal myoblasts (SkM), or 10(6) skeletal myoblasts transfected with Ad(5)RSVVEGF-165 (SkM(+)) into the left ventricle 1week before ischemia. Left ventricle end-diastolic pressure, scar area, and capillary density were assessed 4weeks later.