A5091701527- Heart Failure Treatment and Management
- Pulmonary Hypertension Research and Treatments
- Neuropeptides and Animal Physiology
- Cardiac, Anesthesia and Surgical Outcomes
- Pregnancy and preeclampsia studies
- Cardiovascular Function and Risk Factors
- Phosphodiesterase function and regulation
- Drug Transport and Resistance Mechanisms
- Cardiac Ischemia and Reperfusion
- Heme Oxygenase-1 and Carbon Monoxide
- Intensive Care Unit Cognitive Disorders
- Sepsis Diagnosis and Treatment
- Cardiac Fibrosis and Remodeling
- Aortic Disease and Treatment Approaches
- Adenosine and Purinergic Signaling
- Heart Rate Variability and Autonomic Control
- Aortic aneurysm repair treatments
- Adipose Tissue and Metabolism
- Hemoglobin structure and function
- Receptor Mechanisms and Signaling
- Antibiotics Pharmacokinetics and Efficacy
- Infectious Aortic and Vascular Conditions
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Reproductive System and Pregnancy
- Renin-Angiotensin System Studies
Queen Mary University of London
2015-2025
William Harvey Research Institute
2015-2025
Royal London Hospital
2025
University College London
2011-2014
Barts Health NHS Trust
2014
University of Edinburgh
2009-2013
Rutgers New Jersey Medical School
2013
University of Milan
2013
Istituto Neurologico Mediterraneo
2013
Rutgers, The State University of New Jersey
2013
The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic pressure, and the reactivity of leukocytes platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, stroke. Herein, we evaluated mice with endothelial-specific deletion Nppc, which encodes C-type natriuretic peptide (CNP), determined this mediator is essential for multiple...
Abstract Aims C-type natriuretic peptide (CNP) is an essential endothelium-derived signalling species that governs vascular homoeostasis; CNP also expressed in the heart but intrinsic role for cardiac function not established. Herein, we employ unique transgenic strains with cell-specific deletion of to define a central (patho)physiological capacity maintaining morphology and contractility. Methods results Cardiac structure were explored wild type (WT), cardiomyocyte (cmCNP−/−), endothelium...
The recently discovered cytoprotective action of CO has raised interest in exogenous CO-releasing materials (CORMs) such as metal carbonyls (CO complexes transition metals). To achieve control on delivery with carbonyls, we synthesized and characterized three Mn(I) namely, [Mn(tpa)(CO)3]ClO4 [1, where tpa = tris(2-pyridyl)amine], [Mn(dpa)(CO)3]Br [2, dpa N,N-bis(2-pyridylmethyl)amine], [Mn(pqa)(CO)3]ClO4 [3, pqa (2-pyridylmethyl)(2-quinolylmethyl)amine], by crystallography various...
Angiogenesis and vascular remodeling are complementary, innate responses to ischemic cardiovascular events, including peripheral artery disease myocardial infarction, which restore tissue blood supply oxygenation; the endothelium plays a critical function in these intrinsic protective processes. C-type natriuretic peptide (CNP) is fundamental endothelial signaling species that coordinates homeostasis. Herein, we sought delineate central role for CNP angiogenesis response ischemia.The vitro...
Significance The morbidity and mortality associated with heart failure (HF) are unacceptably high. Cyclic guanosine-3′,5′-monophosphate (cGMP) plays a key role in preserving cardiac structure function, therapeutically targeting cGMP HF has shown promise experimental models patients. Phosphodiesterases (PDEs) metabolize curtail the actions of (and cAMP), increased PDE activity is thought to contribute pathogenesis. Herein, we show that inhibition one specific isoform, PDE2, enhances salutary...
Patients with CKD requiring dialysis have a higher risk of sepsis and 100-fold mortality rate than the general population sepsis. The severity cardiac dysfunction predicts in patients Here, we investigated effect preexisting on function mice whether inhibition I κ B kinase (IKK) reduces Male C57BL/6 underwent 5/6 nephrectomy, 8 weeks later, they were subjected to LPS (2 mg/kg) or by cecal ligation puncture (CLP). Compared sham operation, nephrectomy resulted significant increases urea...
A photoactive manganese carbonyl complex namely, fac-[Mn(pqa)(CO)3]ClO4 (abbreviated as {Mn–CO}, pqa = (2-pyridylmethyl)(2-quinolylmethyl)amine) has been incorporated in the pores of 60 nm mesoporous Al-MCM-41 nanoparticles. Strong electrostatic interactions with negatively charged walls aluminosilicate host entrap cationic resulting material {Mn–CO}@Al-MCM-41 which characterized by various physical techniques and chemical analysis. The sample morphology microstructure have established...
Thermogenesis and adipogenesis are tightly regulated mechanisms that maintain lipid homeostasis energy balance; dysfunction of these critical processes underpins obesity contributes to cardiometabolic disease. C-type natriuretic peptide (CNP) fulfills a multimodal protective role in the cardiovascular system governing local blood flow, angiogenesis, cardiac function, immune cell reactivity. Herein, we investigated parallel, preservative function for CNP coordinating metabolic homeostasis....
C2238 atrial natriuretic peptide (ANP) minor allele (substitution of thymidine with cytosine in position 2238) associates increased risk cardiovascular events.We investigated the mechanisms underlying vascular effects C2238-αANP.In vitro, human umbilical vein endothelial cell were exposed to either wild-type (T2238)- or mutant (C2238)-αANP. Cell survival and apoptosis tested by Trypan blue, annexin V, cleaved caspase-3 assays. C2238-αANP significantly reduced apoptosis. In addition, tube...
BACKGROUND: Thoracic aortic aneurysm (AA) and abdominal AA are life-threatening diseases characterized by dilation, inflammation, structural weakness; development of pharmacological therapies is desperately needed. CNP (C-type natriuretic peptide) plays a key role in vascular homeostasis, mediating vasodilator, anti-inflammatory, antiatherogenic actions. Because such processes drive AA, we determined the endogenous offsetting pathogenesis. METHODS: Tissue from patients with was analyzed to...
Pulmonary arterial hypertension (PAH) is an incurable, incapacitating disorder resulting from increased pulmonary vascular resistance, remodelling, and right ventricular failure. In preclinical models, the combination of a PDE5 inhibitor (PDE5i) with neprilysin augments natriuretic peptide bioactivity, promotes cGMP signalling, reverses structural haemodynamic deficits that characterize PAH. Herein, we conducted randomized, double-blind, placebo-controlled trial to assess efficacy safety...
The present study examined the effect of C-type natriuretic peptide (CNP) and biomechanical signals on anabolic catabolic activities in chondrocyte/agarose constructs.Natriuretic (Npr) 2 3 expression were compared non-diseased (grade 0/1) diseased IV) human cartilage by immunofluoresence microscopy western blotting. In separate experiments, constructs cultured under free-swelling conditions or subjected to dynamic compression with CNP, interleukin-1β (IL-1β), Npr2 antagonist P19 Npr3 agonist...
Background and Purpose cGMP underpins the bioactivity of NO natriuretic peptides is key to cardiovascular homeostasis. cGMP‐driven responses are terminated primarily by PDEs, but cellular efflux via multidrug resistance proteins (MRPs) might contribute. Herein, effect pharmacological blockade MRPs on signalling in heart vasculature was investigated vitro vivo . Experimental Approach Proliferation human coronary artery smooth muscle cells (hCASMCs), vasorelaxation murine aorta reductions mean...
New Findings What is the central question of this study? Does genetic ablation neurokinin‐1 receptors alter arterial blood pressure? main finding and its importance? NK1R −/− mice have increased mean pressure, but without a concomitant change in vascular reactivity. This suggests that play role neural regulation pressure. Mice with functional receptor gene, Tacr1 , ( ) express behavioural abnormalities equivalent to those seen attention deficit hyperactivity disorder (ADHD). An established...
Background and Purpose SER100 is a selective nociceptin (NOP) receptor agonist with sodium‐potassium‐sparing aquaretic anti‐natriuretic activity. This study was designed to characterize the functional cardiovascular pharmacology of in vitro vivo , including experimental models disease. Experimental Approach Haemodynamic, ECG parameters heart rate variability (HRV) were determined using radiotelemetry healthy, conscious mice. The haemodynamic vascular effects also evaluated two disease,...
Objective: To investigate the vascular functional activity, localisation and expression of B1 B2 kinin receptors in normal pregnancy pre-eclampsia. Methods: Kinin receptor-mediated relaxation myometrial arteries was assessed using wire myography. Immunohistochemical staining gene myometrium determined. Results: reduced observed a proportion healthy women impaired Receptor unaltered Conclusion: Here, we demonstrate novel vasodilatation vessels that is absent
Abstract K ATP channels in the vasculature composed of Kir6.1 regulate vascular tone and may contribute to pathogenesis endotoxemia. We used mice with cell-specific deletion smooth muscle (smKO) endothelium (eKO) investigate this question. found that smKO had a significant survival disadvantage compared their littermate controls when treated sub-lethal dose lipopolysaccharide (LPS). All cohorts became hypotensive following bacterial LPS administration; however, mean arterial pressure WT...
<p class="first" dir="auto" id="d1142314e130">Sepsis is one of the leading causes death worldwide yet there are limited treatment options for this disease. There has been increasing interest in therapies targeting microvasculature to improve tissue perfusion and reduce organ damage that often persists despite macrohemodynamic stabilization. CNP a cardioprotective vasodilator peptide shown regulate blood pressure, inflammation, cardiac contractility. Plasma levels elevated patients with...
C-type natriuretic peptide (CNP) is a significant player in the maintenance of cardiac and vascular homeostasis regulating local blood flow, platelet leukocyte activation, heart structure function, angiogenesis metabolic balance. Since such processes are perturbed myocardial infarction (MI), we explored role cardiomyocyte-derived CNP, pharmacological administration peptide, offsetting pathological consequences MI.
Cellular levels of cyclic GMP (cGMP) are tightly controlled by synthetic and degradative mechanisms. Pharmacological manipulation these processes (e.g. soluble guanylate cyclase stimulators phosphodiesterase 5 inhibitors) augments cGMP-dependent signalling is beneficial in treating cardiovascular disease (eg. pulmonary hypertension). An additional mechanism potentially important the inactivation cGMP cellular extrusion, driven a family multidrug resistance proteins (MRPs). Herein, we...
Background: Endothelium-derived C-type natriuretic peptide (CNP) plays a key vascular homeostatic role governing tone, blood pressure, leukocyte flux, platelet reactivity and the integrity of vessel wall. However, relatively little is known about physiological role(s) for endogenous CNP in regulating cardiac structure function. Herein, we have utilised novel mouse strains with endothelium or cardiomyocyte -specific deletion to determine if modulates heart function under basal conditions...