OBJECTIVES: This study sought to measure muscle sympathetic nerve activity (MSNA) in patients with aortic stenosis (AS) before and after transcatheter aortic valve implantation (TAVI) and to compare MSNA with that of control patients. BACKGROUND: TAVI is an emerging therapeutic option in patients with severe AS at high risk of open heart surgery. Whether patients with AS have increased sympa...

BACKGROUND: Tendinopathy is a clinical diagnosis of localised tendon pain often confirmed by imaging findings. The pathophysiological cause of the pain is unknown and the sympathetic nervous system (SNS) may be implicated. OBJECTIVE: To review what is known regarding the role of the SNS in human tendinopathy. STUDY SELECTION: Published data describing sympathetic innervation or an index of...

Cardiomyocyte hypertrophy requires a source of Ca(2+) distinct from the Ca(2+) that regulates contraction. The canonical transient receptor potential channel (TrpC) family, a family of cation channels regulated by activation of phospholipase C (PLC), has been implicated in this response. Cardiomyocyte hypertrophy downstream of Gq-coupled receptors is mediated specifically by PLCβ1b that is scaf...

The lineage of the Y chromosome accounts for up to 15 to 20 mm Hg in arterial pressure. Genes located on the Y chromosome from the spontaneously hypertensive rat (SHR) are associated with the renin-angiotensin system. Given the important role of the renin-angiotensin system in the renal regulation of fluid homeostasis and arterial pressure, we hypothesized that the origin of the Y chromosome in...

Seleno-organic glutathione peroxidase (GPx) mimetics, including ebselen (Eb), have been tested in in vitro studies for their ability to scavenge reactive oxygen and nitrogen species, including hydrogen peroxide and peroxynitrite. In this study, we investigated the efficacies of two Eb analogues, m-hydroxy ebselen (ME) and ethanol-ebselen (EtE) and compared these with Eb in cell based assays. We...

Although detrimental associations of sitting time and health indicators have been observed in young adults, evidence of pathophysiological mechanisms is lacking. Therefore, this study tested the hypothesis that the acute cardiometabolic effects of prolonged sitting can be compensated by hourly interruptions to sitting in healthy, young adults. Additionally, leg muscle activation during sitting ...

BACKGROUND: To examine whether the recent flattening of mortality rates for coronary heart disease (CHD) observed among young adults in the UK and the US is also occurring in the Australian population. METHODS: Mortality data from 1976 to 2006 were used to calculate overall age-adjusted and age-specific mortality rates for Australian adults aged ≥ 25 years. Joinpoint regression was fitted to...

AIMS: Percutaneous coronary intervention (PCI) and catheter ablation are well-accepted therapeutic interventions for treatment of coronary artery disease and atrial fibrillation (AF), respectively. We sought to examine temporal trends in the provision of these services over the past decade in Australia. METHODS AND RESULTS: A retrospective review of the numbers of PCIs and AF ablations from ...

BACKGROUND: In the general population, excessive sedentary behaviour is associated with increased all-cause mortality. Few studies have examined this relationship in people with cardiovascular disease (CVD). Using a sample of people with CVD who were excluded from an analysis of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study, we examined the relationship between sedentary beh...

Bacterial endotoxins have been associated with chronic inflammation and the development and progression of diabetic nephropathy. We hypothesized that subjects with high serum lipopolysaccharide activity also carry remains of bacterial DNA in their system. Serum-derived bacterial DNA clones were isolated and identified from 10 healthy controls and 14 patients with type 1 diabetes (T1D) using uni...

One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between statin-induced expression of muscle atrophy genes, r...

Pathogens-induced platelet activation contributes to inflammation in cardiovascular diseases, but underlying mechanisms remain elusive. Staphylococcal superantigen-like protein 5 (SSL5) is a known activator of platelets. Here we examined whether SSL5 is implicated in Staphylococcus aureus (S. aureus)-induced inflammation and potential mechanisms involved. As expected, we show that SSL5 activate...

Myocardial fibrosis is regarded as a pivotal proarrhythmic substrate, but there have been no comprehensive studies showing a correlation between the severity of fibrosis and ventricular tachyarrhythmias (VTAs). Our purpose was to document this relationship in a transgenic (TG) strain of mice with fibrotic cardiomyopathy. TG mice with cardiac overexpression of β2-adrenoceptors (β2-AR mice) and n...

The transforming growth factor-β (TGF-β) network of ligands and intracellular signaling proteins is a subject of intense interest within the field of skeletal muscle biology. To define the relative contribution of endogenous TGF-β proteins to the negative regulation of muscle mass via their activation of the Smad2/3 signaling axis, we used local injection of adeno-associated viral vectors (AAVs...

OBJECTIVE: ABCA1 (ATP-binding cassette transporter A1) is the principal protein responsible for cellular cholesterol efflux. Abundance and functionality of ABCA1 is regulated both transcriptionally and post-translationally, with endocytosis of ABCA1 being an important element of post-translational regulation. Functional ABCA1 resides on the plasma membrane but can be internalized and either ...

Nitric oxide influences intramuscular signaling that affects skeletal muscle glucose uptake during exercise. The role of the main NO-producing enzyme isoform activated during skeletal muscle contraction, neuronal nitric oxide synthase-μ (nNOSμ), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically cathete...

Imaging of activated platelets using an activation specific anti-GPIIb/IIIa integrin single-chain antibody (scFvanti-LIBS) conjugated to a positron emitting copper-64 complex of a cage amine sarcophagine chelator (MeCOSar) is reported. This tracer was compared in vitro to a (64)Cu(II) complex of the scFv conjugated to another commonly used macrocycle, DOTA. The scFvanti-LIBS-MeCOSar conjugate w...

There is increasing evidence that regular intense endurance exercise can promote structural and electrical remodeling of the right ventricle (RV). These physiological changes can be profound and are frequently accompanied by ECG changes in the right precordial leads, thereby mimicking features observed in arrhythmogenic right ventricular cardiomyopathy (ARVC). Because the 12-lead ECG is used as...

AIMS: To investigate whether diabetes self-care attitudes, behaviours and perceived burden, particularly related to weight management, diet and physical activity, differ between adults with Type 2 diabetes who are severely obese and matched non-severely obese control subjects. METHODS: The 1795 respondents to the Diabetes MILES--Australia national survey had Type 2 diabetes and reported heig...

BACKGROUND AND PURPOSE: Annexin-A1 (ANX-A1) is an endogenous, glucocorticoid-regulated anti-inflammatory protein. The N-terminal-derived peptide Ac-ANX-A1(2-26) preserves cardiomyocyte viability, but the impact of ANX-A1-peptides on cardiac contractility is unknown. We now test the hypothesis that ANX-A1 preserves post-ischaemic recovery of left ventricular (LV) function. EXPERIMENTAL APPROACH...