Sympathetic-transduction in untreated hypertension.

Transduction of muscle sympathetic nerve activity (MSNA) into vascular tone varies with age and sex. Older normotensive men have reduced sympathetic transduction so that a given level of MSNA causes less arteriole vasoconstriction. Whether sympathetic transduction is altered in hypertension (HTN) is not known.

Retrograde blood flow in the internal jugular veins of humans with hypertension may have implications for cerebral arterial blood flow.

Objectives: To use multi-parametric magnetic resonance imaging (MRI) to test the hypothesis that hypertensives would have higher retrograde venous blood flow (RVBF) in the internal jugular veins (IJV) vs. normotensives, and that this would inversely correlate with arterial inflow and gray matter, white matter, and cerebrospinal fluid volumes.

Methods: Following local institutional review board approval and written consent, a prospective observational 3-T MRI study of 42 hypertensive patients (53 ± 2 years, BMI 28.

Loss of IGF1R in Human Astrocytes Alters Complex I Activity and Support for Neurons.

The insulin/insulin-like growth factor 1 (IGF1) signaling pathways are implicated in longevity and in progression of Alzheimer's disease. Previously, we showed that insulin-like growth factor 1 receptor (IGF1R) and downstream signaling transcripts are reduced in astrocytes in human brain with progression of Alzheimer's neuropathology and developed a model of IGF1 signaling impairment in human astrocytes using an IGF1R-specific monoclonal antibody, MAB391. Here, we have established a novel human astrocyte-neuron co-culture system to determine whether loss of astrocytic IGF1R affects their support for neurons.

Noctural dipping status and left ventricular hypertrophy: A cardiac magnetic resonance imaging study.

We investigate the impact of dipper status on cardiac structure with cardiovascular magnetic resonance (CMR). Ambulatory blood pressure monitoring and 1.5T CMR were performed in 99 tertiary hypertension clinic patients.

The Relationship Between Left Ventricular Wall Thickness, Myocardial Shortening, and Ejection Fraction in Hypertensive Heart Disease: Insights From Cardiac Magnetic Resonance Imaging.

Hypertensive heart disease is often associated with a preserved left ventricular ejection fraction despite impaired myocardial shortening. The authors investigated this paradox in 55 hypertensive patients (52±13 years, 58% male) and 32 age- and sex-matched normotensive control patients (49±11 years, 56% male) who underwent cardiac magnetic resonance imaging at 1.5T.

Unilateral Carotid Body Resection in Resistant Hypertension: A Safety and Feasibility Trial.

Animal and human data indicate pathological afferent signaling emanating from the carotid body that drives sympathetically mediated elevations in blood pressure in conditions of hypertension. This first-in-man, proof-of-principle study tested the safety and feasibility of unilateral carotid body resection in 15 patients with drug-resistant hypertension. The procedure proved to be safe and feasible.

Comprehensive First-Line Magnetic Resonance Imaging in Hypertension: Experience From a Single-Center Tertiary Referral Clinic.

European guidelines recommend that patients with hypertension be assessed for asymptomatic organ damage and secondary causes. The authors propose that a single magnetic resonance imaging (MRI) scan can provide comprehensive first-line imaging of patients assessed via a specialist hypertension clinic. A total of 200 patients (56% male, aged 51±15 years, office BP 168±30/96±16 mm Hg) underwent MRI of the heart, kidneys, renal arteries, adrenals and aorta.

Is High Blood Pressure Self-Protection for the Brain?

Rationale: Data from animal models of hypertension indicate that high blood pressure may develop as a vital mechanism to maintain adequate blood flow to the brain. We propose that congenital vascular variants of the posterior cerebral circulation and cerebral hypoperfusion could partially explain the pathogenesis of essential hypertension, which remains enigmatic in 95% of patients.

Objective: To evaluate the role of the cerebral circulation in the pathophysiology of hypertension.

Purinergic receptors in the carotid body as a new drug target for controlling hypertension.

In view of the high proportion of individuals with resistance to antihypertensive medication and/or poor compliance or tolerance of this medication, new drugs to treat hypertension are urgently needed. Here we show that peripheral chemoreceptors generate aberrant signaling that contributes to high blood pressure in hypertension. We discovered that purinergic receptor P2X3 (P2rx3, also known as P2x3) mRNA expression is upregulated substantially in chemoreceptive petrosal sensory neurons in rats with hypertension.

Hypertensive heart disease versus hypertrophic cardiomyopathy: multi-parametric cardiovascular magnetic resonance discriminators when end-diastolic wall thickness ≥ 15 mm.

Objectives: European guidelines state left ventricular (LV) end-diastolic wall thickness (EDWT) ≥15mm suggests hypertrophic cardiomyopathy (HCM), but distinguishing from hypertensive heart disease (HHD) is challenging. We identify cardiovascular magnetic resonance (CMR) predictors of HHD over HCM when EDWT ≥15mm.

Methods: 2481 consecutive clinical CMRs between 2014 and 2015 were reviewed.

ECG strain pattern in hypertension is associated with myocardial cellular expansion and diffuse interstitial fibrosis: a multi-parametric cardiac magnetic resonance study.

Aims: In hypertension, the presence of left ventricular (LV) strain pattern on 12-lead electrocardiogram (ECG) carries adverse cardiovascular prognosis. The underlying mechanisms are poorly understood. We investigated whether hypertensive ECG strain is associated with myocardial interstitial fibrosis and impaired myocardial strain, assessed by multi-parametric cardiac magnetic resonance (CMR).

Comprehensive characterisation of hypertensive heart disease left ventricular phenotypes.

Objective: Myocardial intracellular/extracellular structure and aortic function were assessed among hypertensive left ventricular (LV) phenotypes using cardiovascular magnetic resonance (CMR).

Methods: An observational study from consecutive tertiary hypertension clinic patients referred for CMR (1.5 T) was performed.

Controversies Surrounding Renal Denervation: Lessons Learned From Real-World Experience in Two United Kingdom Centers.

Renal denervation (RDN) is a therapy that targets treatment-resistant hypertension (TRH). The Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity) HTN-1 and Symplicity HTN-2 trials reported response rates of >80%; however, sham-controlled Symplicity HTN-3 failed to reach its primary blood pressure (BP) outcome. The authors address the current controversies surrounding RDN, illustrated with real-world data from two centers in the United Kingdom.

Diagnosis and Management of Iron Deficiency in CKD: A Summary of the NICE Guideline Recommendations and Their Rationale.

The UK-based National Institute for Health and Care Excellence (NICE) has updated its guidance on iron deficiency and anemia management in chronic kidney disease. This report outlines the recommendations regarding iron deficiency and their rationale. Serum ferritin alone or transferrin saturation alone are no longer recommended as diagnostic tests to assess iron deficiency.

Prevalence and predictors of asymmetric hypertensive heart disease: insights from cardiac and aortic function with cardiovascular magnetic resonance.

Aims: We sought to determine the prevalence of asymmetric hypertensive heart disease (HHD) overlapping morphologically with hypertrophic cardiomyopathy (HCM) and to determine predictors of this pattern of hypertensive remodelling.

Methods And Results: One hundred and fifty hypertensive patients underwent 1.5 T cardiovascular magnetic resonance imaging.

The nuclear retention of transcription factor FOXO3a correlates with a DNA damage response and increased glutamine synthetase expression by astrocytes suggesting a neuroprotective role in the ageing brain.

The accumulation of reactive oxygen species leading to oxidative damage and cell death plays an important role in a number of neurodegenerative disorders. FOXO3a, the main isoform of FOXO transcription factors, mediates the cellular response to oxidative stress by regulating the expression of genes involved in DNA repair and glutamine metabolism, including glutamine synthetase (GS). Immunohistochemical investigation of the population-based neuropathology cohort of the Medical Research Council's Cognitive Function and Ageing Study (MRC CFAS) demonstrates that nuclear retention of FOXO3a significantly correlates with a DNA damage response and with GS expression by astrocytes.

Insulin and IGF1 signalling pathways in human astrocytes in vitro and in vivo; characterisation, subcellular localisation and modulation of the receptors.

Background: The insulin/IGF1 signalling (IIS) pathways are involved in longevity regulation and are dysregulated in neurons in Alzheimer's disease (AD). We previously showed downregulation in IIS gene expression in astrocytes with AD-neuropathology progression, but IIS in astrocytes remains poorly understood. We therefore examined the IIS pathway in human astrocytes and developed models to reduce IIS at the level of the insulin or the IGF1 receptor (IGF1R).

Neuronal DNA damage response-associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of Alzheimer-type pathology.

Aims: Oxidative damage and an associated DNA damage response (DDR) are evident in mild cognitive impairment and early Alzheimer's disease, suggesting that neuronal dysfunction resulting from oxidative DNA damage may account for some of the cognitive impairment not fully explained by Alzheimer-type pathology.

Methods: Frontal cortex (Braak stage 0-II) was obtained from the Medical Research Council's Cognitive Function and Ageing Study cohort. Neurones were isolated from eight cases (four high and four low DDR) by laser capture microdissection and changes in the transcriptome identified by microarray analysis.

Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models.

Resistance to targeted EGFR inhibitors is likely to develop in EGFR-mutant lung cancers. Early identification of innate or acquired resistance mechanisms to these agents is essential to direct development of future therapies. We describe the detection of heterogeneous mechanisms of resistance within populations of EGFR-mutant cells (PC9 and/or NCI-H1975) with acquired resistance to current and newly developed EGFR tyrosine kinase inhibitors, including AZD9291.

Deep brain stimulation for the treatment of resistant hypertension.

Hypertension is a leading risk factor for the development of several cardiovascular diseases. As the global prevalence of hypertension increases, so too has the recognition of resistant hypertension. Whilst figures vary, the proportion of hypertensive patients that are resistant to multiple drug therapies have been reported to be as high as 16.

Revelations about carotid body function through its pathological role in resistant hypertension.

Much recent attention has been given to the carotid body because of its potential role in cardiovascular disease states. One disease, neurogenic hypertension, characterised by excessive sympathetic activity, appears dependent on carotid body activity that may or may not be accompanied by sleep-disordered breathing. Herein, we review recent literature suggesting that the carotid body acquires tonicity in hypertension.