Rhian Touyz

Rhian Touyz
University of Glasgow | UofG · Institute of Cardiovascular and Medical Sciences

MBBCh, PhD, FRSE, FRCP

About

920
Publications
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Publications

Publications (920)
Article
Growing interest surrounds the assessment of perivascular spaces (PVS) on magnetic resonance imaging (MRI) and their validation as a clinical biomarker of adverse brain health. Nonetheless, the limits of validity of current state-of-the-art segmentation methods are still unclear. Here, we propose an open-source three-dimensional computational frame...
Article
Full-text available
Hyperaldosteronism causes cardiovascular disease as well as hypomagnesemia. Mechanisms are ill-defined but dysregulation of TRPM7, a Mg ²⁺ -permeable channel/α-kinase, may be important. We examined the role of TRPM7 in aldosterone-dependent cardiovascular and renal injury by studying aldosterone-salt treated TRPM7-deficient (TRPM7 +/Δkinase ) mice....
Article
Full-text available
Purpose Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent group...
Article
Mice expressing human Nox5 (hNox5) in vascular smooth muscle cells (VSMC) exhibit redox-sensitive vascular dysfunction and cardio-renal fibrosis. Mechanisms underlying pro-fibrotic effects are unclear. Here we assessed whether hNox5 in VSMCs promotes fibroblast phenotypic changes leading to myofibroblast differentiation and pro-fibrotic/inflammator...
Article
Phenotypic switching of vascular smooth muscle cells (VSMCs) is a fundamental process in vascular dysfunction and remodeling associated with hypertension. Mechanisms underlying this process involve reactive oxygen species (ROS) and redox-dependent signaling pathways. However, the proteomic signature and effects of ROS on VSMC proteome in human hype...
Article
COVID19-associated immunopathology is associated with increased production of interferon (IFN)-alpha (IFNα) and lambda3 (IFNL3). Effects of IFNs are mediated by interferon-stimulated genes (ISGs) and influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. Increasing evidence indicates vascular...
Article
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Introduction COVID-19 may lead to long-term endothelial consequences including hypertension, stroke and myocardial infarction. A pilot study ‘COVID-19 blood pressure endothelium interaction study’, which found that patients with normal blood pressure (BP) at the time of hospital admission with COVID-19 showed an 8.6 mm Hg higher BP ≥12 weeks after...
Article
The pathophysiology and trajectory of post-Coronavirus Disease 2019 (COVID-19) syndrome is uncertain. To clarify multisystem involvement, we undertook a prospective cohort study including patients who had been hospitalized with COVID-19 (ClinicalTrials.gov ID NCT04403607). Serial blood biomarkers, digital electrocardiography and patient-reported ou...
Poster
Full-text available
Background: Long-term exposure to cardiovascular risk factors can harm cerebral micro-vessels, causing endothelial dysfunction and damaging the brain parenchyma. Visibility of perivascular spaces (PVS) on MRI is thought to be an early feature. Here, we investigate whether common cardiovascular risk factors (BP, smoking, diabetes) predict PVS burde...
Article
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Vascular endothelial growth factor antagonism with angiogenesis inhibitors in cancer patients induces a "preeclampsia-like" syndrome including hypertension, proteinuria and elevated endothelin (ET)-1. Cyclo-oxygenase (COX) inhibition with aspirin is known to prevent the onset of preeclampsia in high-risk patients. In the present study we hypothesis...
Article
Aims Hypogonadism is associated with cardiovascular disease. However, the cardiovascular impact of hypogonadism during development is unknown. Using hypospadias as a surrogate of hypogonadism, we investigated whether hypospadias is associated with vascular dysfunction and is a risk factor for cardiovascular disease. Methods and results Our human s...
Article
Excessive production of renal reactive oxygen species (ROS) play a major role in diabetic kidney disease (DKD). Here, we provide key novel findings demonstrating the predominant pathological role of the prooxidant enzyme NADPH oxidase-NOX5 in DKD, independent of the previously characterised NOX4 pathway. In diabetic patients, we found increased exp...
Article
Exosomes, which are membrane-bound extracellular vesicles (EVs), are generated in the endosomal compartment of almost all eukaryotic cells. They are formed upon the fusion of multivesicular bodies and the plasma membrane and carry proteins, nucleic acids, lipids and other cellular constituents from their parent cells. Multiple factors influence the...
Article
Full-text available
Current research on hypertension utilizes more than fifty animal models that rely mainly on stable increases in systolic blood pressure. In experimental hypertension, grading or scoring of glomerulopathy in the majority of studies is based on a wide range of opinion-based histological changes that do not necessarily comply with lesional descriptors...
Chapter
Hypertension is a complex, multifactorial and multisystem disorder and a leading cause of morbidity and premature death globally. Major guidelines define it as systolic blood pressure > 130 mmHg and/or diastolic blood pressure > 80 mmHg. Hypertension is a very common disease with prevalence rates of about 30% in adults worldwide. The incidence of h...
Article
Full-text available
Document Reviewers: Rudolf A. de Boer (CPG Review Coordinator) (Netherlands), P. Christian Schulze (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Johann Bauersachs (Germany), Antoni Bayes-Genis (Spain)...
Chapter
Hypertension is a common disorder and a major risk factor for cardiovascular disease. Underlying pathophysiological mechanisms include increased vascular resistance, determined primarily by endothelial dysfunction, vascular hyperreactivity, and arterial remodeling, features that characterize the vascular phenotype in hypertension. Myriad molecular...
Article
Nonalcoholic steatohepatitis (NASH) is a progressive liver disease and has become a leading indication for liver transplantation in the United States. The development of effective therapies for NASH is a major unmet need. Here, we identified a small molecule, IMA-1, that can treat NASH by interrupting the arachidonate 12-lipoxygenase (ALOX12)-acety...
Article
Lipotoxicity is a recognized pathological trigger and accelerator of nonalcoholic steatohepatitis (NASH). However, the molecular basis of lipotoxicity-induced NASH remains elusive. Here, we systematically mapped the changes in hepatic transcriptomic landscapes in response to lipotoxic insults across multiple species. Conserved and robust activation...
Article
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Dramatic improvements in cancer survival have arisen because of the rapid development of novel anti-cancer therapies. The potential for cardiovascular toxicity associated with these drugs often reflects overlap between pathogenic cancer mechanisms and physiological pathways required for normal cardiovascular function. Clinical Science has, therefor...
Article
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Aims Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and mana...
Article
Full-text available
Aims Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and mana...
Article
Full-text available
SARS-CoV-2 viral attachment and entry into host cells is mediated by a direct interaction between viral spike glycoproteins and membrane bound angiotensin-converting enzyme 2 (ACE2). The receptor binding motif (RBM), located within the S1 subunit of the spike protein, incorporates the majority of known ACE2 contact residues responsible for high aff...
Article
Full-text available
Aims Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and mana...
Article
Full-text available
Aims Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and mana...
Preprint
Full-text available
Background: The pathophysiology and trajectory of multiorgan involvement in post-COVID-19 syndrome is uncertain. Methods: A prospective, multicenter, longitudinal, cohort study involving post-COVID-19 patients enrolled in-hospital or early post-discharge (visit 1) and re-evaluated 28-60 days post-discharge (visit 2). Multisystem investigations incl...
Article
Aims Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that induces a reversible post-translational modification (ISGylation) and can also be secreted as a free form. ISG15 plays an essential role as host-defence response to microbial infection; however, its contribution to vascular damage associated with hypertension is unknow...
Article
Hypertension, vascular dysfunction and downregulation of the renin angiotensin system as sequelae of COVID-19 The long-term CV consequences of COVID are unknown however the potential for ongoing cardiac and vascular inflammation with RAAS alteration may increase the risk of developing hypertension and CV disease. Non-hypertensive patients hospitali...
Article
We demonstrated that Mas1 and ET B R physically interact in endothelial cells inducing Ang-(1-7) vascular protection. Using high throughput screening of >20,000 druggable compounds, we identified a number of molecules that enhance Mas1:ET B R interactions. Of these, 2 potently enhanced interaction between the receptors. These enhancers (Enh), terme...
Article
Vascular smooth muscle cells (VSMCs) are key players in vascular dysfunction associated with hypertension, where phenotypic switch is a fundamental process. While various transcription factors have been implicated in this process, the proteomic signature associated with phenotypic switching in human hypertension is unknown. Using high fidelity prot...
Article
Hypertension is a common unwanted effect of VEGF inhibitors (VEGFi), which are used as anti-angiogenic drugs in cancer treatment. Clinical observations suggest that the combination of VEGFi with another anti-cancer drug, olaparib (PARP inhibitor [PARPi]), may attenuate the development of hypertension. However putative vascular mechanisms are unknow...
Article
SARS-CoV-2, the virus responsible for COVID19, binds to ACE2, via its spike protein S1 subunit, leading to viral infection and respiratory disease. COVID-19 is associated with cardiovascular disease and systemic inflammation. Since ACE2 is expressed in vascular cells we questioned whether SARS-CoV-2 induces vascular inflammation and whether this is...
Article
Introduction: Interferon (IFN) alpha (IFNα) and lambda3 (IFNL3) constitute the first line of immunity against SARS-CoV-2 infection by increasing interferon-stimulated genes (ISGs). IFNs influence the expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. Here we hypothesized that in human microvascular...
Article
High salt diet (HSD) has deleterious effects on the vasculature by mechanisms not fully elucidated. We demonstrated tight coupling between Na ⁺ and Ca ²⁺ levels in VSMCs, where PARP-regulated TRPM2, a redox-sensitive Ca ²⁺ channel, plays an important role. Increased [Ca ²⁺ ]i also contributes to inflammasome assembly, which dysregulates vascular fu...
Article
COVID-19 illness is associated with cardiovascular vulnerabilities at all stages pre-infection, acute phase and subsequent chronic phase. The major cardiometabolic drivers identified to have epidemiological and mechanistic associations with COVID-19 are abnormal adiposity, dysglycaemia, dyslipidaemia, and hypertension. Recent findings demonstrate t...
Article
Full-text available
Aims NOX-derived reactive oxygen species (ROS) are mediators of signaling pathways implicated in vascular smooth muscle cell (VSMC) dysfunction in hypertension. Among the numerous redox-sensitive kinases important in VSMC regulation is c-Src. However, mechanisms linking NOX/ROS to c-Src are unclear, especially in the context of oxidative stress in...
Article
Combined inhibition of NEP (neutral endopeptidase) and ACE (angiotensin-converting enzyme), without unwanted effects, remains an attractive therapeutic strategy in cardiovascular medicine. Omapatrilat, a dual NEP inhibitor–ACE inhibitor, was a promising antihypertensive drug but failed in trials due to angioedema, an effect possibly caused by inhib...
Article
Full-text available
Objective: The mechanisms involved in NOX5 activation in atherosclerotic processes are not completely understood. This study tested the hypothesis that lysophosphatidylcholine (LPC), a proatherogenic component of oxLDL, induces endothelial calcium influx, which drives NOX5-dependent reactive oxygen species (ROS) production, oxidative stress, and e...
Chapter
Current evidence points towards perivascular spaces playing a key role in cerebral haemodynamics and waste clearance. Hence, their precise quantification may become a powerful tool for assessing brain health and further establishing their relationship with neurological diseases. Large strides have been made towards developing automatic tools to com...
Article
Full-text available
Sex hormone receptors are expressed throughout the vasculature and play an important role in the modulation of blood pressure in health and disease. The functions of these receptors may be important in the understanding of sexual dimorphism observed in the pathophysiology of both hypertension and vascular ageing. The interconnectivity of these fact...
Article
Importance Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied. Objective To examine the prevalence of CAD and CMD in hospitalized patie...
Article
Full-text available
The current COVID-19 pandemic, caused by the SARS-CoV-2 virus (Severe Acute Respiratory Syndrome-Coronavirus-2), represents the largest medical challenge in decades. It has exposed unexpected cardiovascular vulnerabilities at all stages of the disease (pre-infection, acute phase and subsequent chronic phase). The major cardiometabolic drivers ident...
Article
A link between oxidative stress and hypertension has been firmly established in multiple animal models of hypertension but remains elusive in humans. While initial studies focused on inactivation of nitric oxide by superoxide, our understanding of relevant reactive oxygen species (superoxide, hydrogen peroxide, and peroxynitrite) and how they modif...
Chapter
The number of patients with cancer-related cardiovascular disorders is increasing. This is attributed to increased survival of cancer patients who live longer (and are thus at risk for age-related cardiovascular disease) and the cardiovascular toxicities of many newer cancer drugs. Anthracyclines have been long associated with the development of di...
Article
Full-text available
Notch3 mutations cause Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoenephalopathy (CADASIL), which predisposes to stroke and dementia. CADASIL is characterized by vascular dysfunction and granular osmiophilic material (GOM) accumulation in cerebral small vessels. Systemic vessels may also be impacted by Notch3 mutatio...
Article
Full-text available
The two axes of the renin–angiotensin system include the classical ACE/Ang II/AT1 axis and the counter-regulatory ACE2/Ang-(1-7)/Mas1 axis. ACE2 is a multifunctional monocarboxypeptidase responsible for generating Ang-(1-7) from Ang II. ACE2 is important in the vascular system where it is found in arterial and venous endothelial cells and arterial...