Robert E. Widdop
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View article: The novel AT2 receptor ligand, β-Pro7 Ang III, induces equivalent anti-fibrotic effects to Compound 21 but broader anti-fibrotic effects than pirfenidone in mice with bleomycin-induced pulmonary fibrosis
The novel AT2 receptor ligand, β-Pro7 Ang III, induces equivalent anti-fibrotic effects to Compound 21 but broader anti-fibrotic effects than pirfenidone in mice with bleomycin-induced pulmonary fibrosis Open
Angiotensin II AT2 receptor (AT2R) activation leads to significant anti-fibrotic and anti-inflammatory effects in diseased organs, which has led to clinical trial evaluation of the AT2R agonist, Compound 21 (C21), as a treatment for idiopa…
View article: The renoprotective efficacy and safety of genetically-engineered human bone marrow-derived mesenchymal stromal cells expressing anti-fibrotic cargo
The renoprotective efficacy and safety of genetically-engineered human bone marrow-derived mesenchymal stromal cells expressing anti-fibrotic cargo Open
Background Kidney fibrosis is a hallmark of chronic kidney disease (CKD) and compromises the viability of transplanted human bone marrow-derived mesenchymal stromal cells (BM-MSCs). Hence, BM-MSCs were genetically-engineered to express the…
View article: Sex- and time-dependent role of insulin regulated aminopeptidase in lipopolysaccharide-induced inflammation
Sex- and time-dependent role of insulin regulated aminopeptidase in lipopolysaccharide-induced inflammation Open
The enzyme, insulin regulated aminopeptidase (IRAP), is expressed in multiple immune cells such as macrophages, dendritic cells and T cells, where it plays a role in regulating the innate and adaptive immune response. There is a genetic as…
View article: Angiotensin-(1-5) is a Potent Endogenous Angiotensin AT<sub>2</sub>-Receptor Agonist
Angiotensin-(1-5) is a Potent Endogenous Angiotensin AT<sub>2</sub>-Receptor Agonist Open
Background The renin-angiotensin system involves many more enzymes, receptors and biologically active peptides than originally thought. With this study, we investigated whether angiotensin-(1-5) [Ang-(1-5)], a 5-amino acid fragment of angi…
View article: The involvement of the Wnt/β-catenin signaling cascade in fibrosis progression and its therapeutic targeting by relaxin
The involvement of the Wnt/β-catenin signaling cascade in fibrosis progression and its therapeutic targeting by relaxin Open
Organ scarring, referred to as fibrosis, results from a failed wound-healing response to chronic tissue injury and is characterised by the aberrant accumulation of various extracellular matrix (ECM) components. Once established, fibrosis i…
View article: N-(Heteroaryl)thiophene sulfonamides as angiotensin AT2 receptor ligands
N-(Heteroaryl)thiophene sulfonamides as angiotensin AT2 receptor ligands Open
Two series of N-(heteroaryl)thiophene sulfonamides, encompassing either a methylene imidazole group or a tert-butylimidazolylacetyl group in the meta position of the benzene ring, have been synthesized. An AT2R selective ligand …
View article: Inhibition of insulin-regulated aminopeptidase confers neuroprotection in a conscious model of ischemic stroke
Inhibition of insulin-regulated aminopeptidase confers neuroprotection in a conscious model of ischemic stroke Open
Stroke is a leading cause of mortality and morbidity with a paucity of effective pharmacological treatments. We have previously identified insulin-regulated aminopeptidase (IRAP) as a potential target for the development of a new class of …
View article: Catch your breath: The protective role of the angiotensin AT2 receptor for the treatment of idiopathic pulmonary fibrosis
Catch your breath: The protective role of the angiotensin AT2 receptor for the treatment of idiopathic pulmonary fibrosis Open
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease whereby excessive deposition of extracellular matrix proteins (ECM) ultimately leads to respiratory failure. While there have been advances in pharmacotherapies…
View article: Novel AT2R agonist, β-Pro7Ang III, is cardio- and vaso-protective in diabetic spontaneously hypertensive rats
Novel AT2R agonist, β-Pro7Ang III, is cardio- and vaso-protective in diabetic spontaneously hypertensive rats Open
Stimulation of the angiotensin II type 2 receptor (AT2R) evokes protective effects in various cardiovascular diseases. Thus, this study aimed to investigate the effects of AT2R stimulation, with or without AT1
View article: The protective effects of a novel AT2 receptor agonist, β-Pro7Ang III in ischemia-reperfusion kidney injury
The protective effects of a novel AT2 receptor agonist, β-Pro7Ang III in ischemia-reperfusion kidney injury Open
Administration of β-Pro7Ang III via mini-pump improved kidney structure and reduced interstitial collagen accumulation, in parallel with an alteration of macrophage phenotype and anti-inflammatory cytokine release, therefore mit…
View article: The single-chain relaxin mimetic, B7-33, maintains the cardioprotective effects of relaxin and more rapidly reduces left ventricular fibrosis compared to perindopril in an experimental model of cardiomyopathy
The single-chain relaxin mimetic, B7-33, maintains the cardioprotective effects of relaxin and more rapidly reduces left ventricular fibrosis compared to perindopril in an experimental model of cardiomyopathy Open
The hormone, relaxin (RLX), exerts various organ-protective effects independently of etiology. However, its complex two-chain and three disulphide bonded structure is a limitation to its preparation and affordability. Hence, a single chain…
View article: <i>N</i>-(Heteroaryl)Thiophene Sulfonamides as Angiotensin AT2 Receptor Ligands
<i>N</i>-(Heteroaryl)Thiophene Sulfonamides as Angiotensin AT2 Receptor Ligands Open
View article: The Severity of Isoproterenol-Induced Myocardial Fibrosis and Related Dysfunction in Mice Is Strain-Dependent
The Severity of Isoproterenol-Induced Myocardial Fibrosis and Related Dysfunction in Mice Is Strain-Dependent Open
The isoproterenol (or isoprenaline; ISO)-induced model of myocardial injury provides a non-surgical means of establishing features of dilated cardiomyopathy (DCM) in various species, including left ventricular (LV) inflammation, cardiomyoc…
View article: Functional crosstalk between angiotensin receptors (types 1 and 2) and relaxin family peptide receptor 1 (RXFP1): Implications for the therapeutic targeting of fibrosis
Functional crosstalk between angiotensin receptors (types 1 and 2) and relaxin family peptide receptor 1 (RXFP1): Implications for the therapeutic targeting of fibrosis Open
Class A, rhodopsin‐like, G‐protein‐coupled receptors (GPCRs) are by far the largest class of GPCRs and are integral membrane proteins used by various cells to convert extracellular signals into intracellular responses. Initially, class A G…
View article: The protective effects of a novel AT2 receptor agonist, β-Pro7 Ang III in ischemia-reperfusion kidney injury
The protective effects of a novel AT2 receptor agonist, β-Pro7 Ang III in ischemia-reperfusion kidney injury Open
Background and Purpose: This study investigated the reno-protective effects of a highly selective AT2R agonist peptide, β-Pro7Ang III in a mouse model of acute kidney injury (AKI). Experimental Approach: C57BL/6J mice underwent either sham…
View article: The Novel AT2 Receptor Agonist β-Pro7-AngIII Exerts Cardiac and Renal Anti-Fibrotic and Anti-Inflammatory Effects in High Salt-Fed Mice
The Novel AT2 Receptor Agonist β-Pro7-AngIII Exerts Cardiac and Renal Anti-Fibrotic and Anti-Inflammatory Effects in High Salt-Fed Mice Open
A high salt (HS) diet is associated with an increased risk for cardiovascular diseases (CVDs) and fibrosis is a key contributor to the organ dysfunction involved in CVDs. The activation of the renin angiotensin type 2 receptor (AT2R) has b…
View article: The Angiotensin AT2 Receptor: From a Binding Site to a Novel Therapeutic Target
The Angiotensin AT2 Receptor: From a Binding Site to a Novel Therapeutic Target Open
View article: Optimising the photothrombotic model of stroke in the C57BI/6 and FVB/N strains of mouse
Optimising the photothrombotic model of stroke in the C57BI/6 and FVB/N strains of mouse Open
View article: Optimising the Photothrombotic Model of Stroke in the C57BI/6 and FVB/N Strains of Mouse
Optimising the Photothrombotic Model of Stroke in the C57BI/6 and FVB/N Strains of Mouse Open
The photothrombotic stroke model relies on the interaction between photosensitive-dye and light for clot formation. Interestingly, the relationship between the length of light exposure and stroke-outcome has never been examined. This model…
View article: Comparing the renoprotective effects of BM-MSCs versus BM-MSC-exosomes, when combined with an anti-fibrotic drug, in hypertensive mice
Comparing the renoprotective effects of BM-MSCs versus BM-MSC-exosomes, when combined with an anti-fibrotic drug, in hypertensive mice Open
View article: Relaxin Attenuates Organ Fibrosis via an Angiotensin Type 2 Receptor Mechanism in Aged Hypertensive Female Rats
Relaxin Attenuates Organ Fibrosis via an Angiotensin Type 2 Receptor Mechanism in Aged Hypertensive Female Rats Open
Key Points Relaxin attenuates tissue fibrosis in an organ- and age-specific manner. The antifibrotic actions of relaxin are mediated via an angiotensin type 2 receptor mechanism. Relaxin replacement therapy is a potential antifibrotic for …
View article: In Aged Females, the Enhanced Pressor Response to Angiotensin II Is Attenuated By Estrogen Replacement via an Angiotensin Type 2 Receptor-Mediated Mechanism
In Aged Females, the Enhanced Pressor Response to Angiotensin II Is Attenuated By Estrogen Replacement via an Angiotensin Type 2 Receptor-Mediated Mechanism Open
Loss of ovarian hormones following menopause contributes to the rise in cardiovascular risk with age. Estrogen plays a protective role against hypertension and end-organ damage by modulating the depressor actions of the AT 2 R (angiotensin…
View article: Preclinical rodent models of cardiac fibrosis
Preclinical rodent models of cardiac fibrosis Open
Cardiac fibrosis (scarring), characterised by an increased deposition of extracellular matrix (ECM) proteins, is a hallmark of most types of cardiovascular disease and plays an essential role in heart failure progression. Inhibition of car…
View article: Using conformational constraints at position 6 of Angiotensin II to generate compounds with enhanced AT2R selectivity and proteolytic stability
Using conformational constraints at position 6 of Angiotensin II to generate compounds with enhanced AT2R selectivity and proteolytic stability Open
View article: Combining mesenchymal stem cells with serelaxin provides enhanced renoprotection against 1K/DOCA/salt‐induced hypertension
Combining mesenchymal stem cells with serelaxin provides enhanced renoprotection against 1K/DOCA/salt‐induced hypertension Open
Background and Purpose Fibrosis is a hallmark of chronic kidney disease (CKD) that significantly contributes to renal dysfunction, and impairs the efficacy of stem cell‐based therapies. This study determined whether combining bone marrow‐d…
View article: N-(Methyloxycarbonyl)thiophene sulfonamides as high affinity AT2 receptor ligands
N-(Methyloxycarbonyl)thiophene sulfonamides as high affinity AT2 receptor ligands Open
View article: Cover Feature: Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity (Chem. Eur. J. 47/2020)
Cover Feature: Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity (Chem. Eur. J. 47/2020) Open
Single peptide backbone surrogate 1,2,3-triazole mutations can regulate angiotensin GPCR subtype selectivity. [Y]6-Angiotensin II analogs with amide bonds replaced by 1,4-disubstituted isosteres illustrated enhanced AT2R/AT1R subtype selec…
View article: Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity
Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity Open
Mutating the side‐chains of amino acids in a peptide ligand, with unnatural amino acids, aiming to mitigate its short half‐life is an established approach. However, it is hypothesized that mutating specific backbone peptide bonds with bioi…
View article: Renal functional effects of the highly selective AT2R agonist, β-Pro7 Ang III, in normotensive rats
Renal functional effects of the highly selective AT2R agonist, β-Pro7 Ang III, in normotensive rats Open
Recently, we designed a group of peptides by sequential substitution of the naturally occurring α-amino acid throughout the Ang III peptide sequence with the corresponding β-amino acid. β-Amino acid substitution at the proline residue of A…
View article: Serelaxin and the AT<sub>2</sub> Receptor Agonist CGP42112 Evoked a Similar, Nonadditive, Cardiac Antifibrotic Effect in High Salt-Fed Mice That Were Refractory to Candesartan Cilexetil
Serelaxin and the AT<sub>2</sub> Receptor Agonist CGP42112 Evoked a Similar, Nonadditive, Cardiac Antifibrotic Effect in High Salt-Fed Mice That Were Refractory to Candesartan Cilexetil Open
Fibrosis is involved in the majority of cardiovascular diseases and is a key contributor to end-organ dysfunction. In the current study, the antifibrotic effects of recombinant human relaxin-2 (serelaxin; RLX) and/or the AT2R ag…