James Leiper
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View article: Heterogeneous metabolic response of endothelial cells from different vascular beds to experimental hyperglycaemia and metformin
Heterogeneous metabolic response of endothelial cells from different vascular beds to experimental hyperglycaemia and metformin Open
Endothelial cells (ECs) are highly glycolytic, with mitochondria primarily serving a signalling function. Metabolic disruptions are early contributors to endothelial dysfunction, a primary feature of diabetic vascular complications, such a…
View article: RWOP2 Heterogeneous metabolic response of endothelial cells from different vascular beds to hyperglycaemia and metformin
RWOP2 Heterogeneous metabolic response of endothelial cells from different vascular beds to hyperglycaemia and metformin Open
Objectives Endothelial cell (EC) dysfunction is a primary feature of diabetes. Those affected are at an increased risk of vascular bed-specific complications such as retinopathy and small vessel disease. ECs are highly glycolytic with mito…
View article: Asymmetric Dimethylarginine Enables Depolarizing Spikes and Vasospasm in Mesenteric and Coronary Resistance Arteries
Asymmetric Dimethylarginine Enables Depolarizing Spikes and Vasospasm in Mesenteric and Coronary Resistance Arteries Open
BACKGROUND: Increased vasoreactivity due to reduced endothelial NO bioavailability is an underlying feature of cardiovascular disease, including hypertension. In small resistance arteries, declining NO enhances vascular smooth muscle (VSM)…
View article: The Calcium-sensing receptor is an important regulator of female visceral and perivascular adipocyte function
The Calcium-sensing receptor is an important regulator of female visceral and perivascular adipocyte function Open
The Calcium-sensing receptor (CaSR) is a G protein-coupled receptor activated by fluctuations in extracellular calcium concentrations. Its importance in calcium homeostasis has long been established, though its role in other tissues is not…
View article: BS21 Metabolic heterogeneity between endothelial cells from different vascular beds
BS21 Metabolic heterogeneity between endothelial cells from different vascular beds Open
Objective Endothelial dysfunction is a primary feature of cardiovascular disease in diabetes. Those with diabetes are at an increased risk of vascular complications associated with specific vascular beds such as retinopathy, poor wound hea…
View article: BS23 The adipocyte calcium-sensing receptor is important is female visceral and perivascular adipose function
BS23 The adipocyte calcium-sensing receptor is important is female visceral and perivascular adipose function Open
Objective The calcium-sensing receptor (CaSR) is a class C GPCR important in the regulation of whole body calcium homeostasis. However, the CaSR is expressed in many tissues unrelated to calcium handling including adipocytes and human adip…
View article: Asymmetric dimethylarginine positively modulates calcium-sensing receptor signalling to promote lipid accumulation
Asymmetric dimethylarginine positively modulates calcium-sensing receptor signalling to promote lipid accumulation Open
Asymmetric dimethylarginine (ADMA) is generated through the irreversible methylation of arginine residues. It is an independent risk factor for cardiovascular disease, currently thought to be due to its ability to act as a competitive inhi…
View article: Asymmetric dimethylarginine positively modulates Calcium-Sensing Receptor signalling to promote lipid accumulation and adiposity
Asymmetric dimethylarginine positively modulates Calcium-Sensing Receptor signalling to promote lipid accumulation and adiposity Open
Irreversible methylation of arginine residues generates asymmetric dimethylarginine (ADMA). ADMA is a competitive inhibitor of nitric oxide (NO) synthase and an independent risk factor for cardiovascular disease. Plasma ADMA concentrations…
View article: Mechanistic interactions of uromodulin with the thick ascending limb: perspectives in physiology and hypertension
Mechanistic interactions of uromodulin with the thick ascending limb: perspectives in physiology and hypertension Open
Hypertension is a significant risk factor for cardiovascular disease and mortality worldwide. The kidney is a major regulator of blood pressure and electrolyte homeostasis, with monogenic disorders indicating a link between abnormal ion tr…
View article: ADMA: A Key Player in the Relationship between Vascular Dysfunction and Inflammation in Atherosclerosis
ADMA: A Key Player in the Relationship between Vascular Dysfunction and Inflammation in Atherosclerosis Open
Atherosclerosis is a chronic cardiovascular disease which increases risk of major cardiovascular events including myocardial infarction and stroke. Elevated plasma concentrations of asymmetric dimethylarginine (ADMA) have long been recogni…
View article: Peer Review #2 of "Transplantation of adipose-derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus-induced erectile dysfunction in rats (v0.1)"
Peer Review #2 of "Transplantation of adipose-derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus-induced erectile dysfunction in rats (v0.1)" Open
Background: Erectile dysfunction is a major complication of diabetes mellitus.Adipose derived stem cells (ADSCs) have attracted much attention as a promising tool for the treatment of diabetes mellitus induced erectile dysfunction (DMED).I…
View article: BS41 Asymmetric dimethylarginine increases calcium sensing receptor signalling to promote endothelial no production
BS41 Asymmetric dimethylarginine increases calcium sensing receptor signalling to promote endothelial no production Open
Objective The post-translational methylation of arginine residues by PRMT enzymes can yield asymmetric dimethylarginine (ADMA); which, following proteolysis is released into the cytosol and enters the circulation. Elevated plasma ADMA conc…
View article: LPS-Induced Hypotension in Pregnancy: The Effect of Progesterone Supplementation
LPS-Induced Hypotension in Pregnancy: The Effect of Progesterone Supplementation Open
Our previous work has shown that pregnancy exacerbates the hypotensive response to both infection and lipopolysaccharide (LPS). The high levels of progesterone (P4) associated with pregnancy have been suggested to be responsible for the pr…
View article: Rapid onset of severe septic shock in the pregnant mouse†
Rapid onset of severe septic shock in the pregnant mouse† Open
Sepsis-related mortality was markedly greater in pregnant mice. Cardiovascular collapse and organ dysfunction occurred sooner in pregnancy, but bacterial killing was similar. Circulating and tissue cytokine levels were similar, but immune …
View article: nNOS-Expressing Neurons in the Ventral Tegmental Area and Substantia Nigra Pars Compacta
nNOS-Expressing Neurons in the Ventral Tegmental Area and Substantia Nigra Pars Compacta Open
GABA neurons in the VTA and SNc play key roles in reward and aversion through their local inhibitory control of dopamine neuron activity and through long-range projections to several target regions including the nucleus accumbens. It is no…
View article: Regulation of fluid reabsorption in rat or mouse proximal renal tubules by asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase 1
Regulation of fluid reabsorption in rat or mouse proximal renal tubules by asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase 1 Open
Nitric oxide prevents hypertension yet enhances proximal tubule Na + reabsorption. Nitric oxide synthase is inhibited by asymmetric dimethylarginine (ADMA) that is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) whose type 1 …
View article: nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta
nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta Open
GABA neurons in the ventral tegmental area (VTA) and substantia nigra pars compact (SNc) play key roles in reward and aversion through their local inhibitory control of dopamine neuron activity and through long-range projections to several…
View article: NRF2 prevents hypertension, increased ADMA, microvascular oxidative stress, and dysfunction in mice with two weeks of ANG II infusion
NRF2 prevents hypertension, increased ADMA, microvascular oxidative stress, and dysfunction in mice with two weeks of ANG II infusion Open
Nuclear factor erythyroid factor 2 (Nrf2) transcribes genes in cultured endothelial cells that reduce reactive oxygen species (ROS) and generate nitric oxide (NO) or metabolize asymmetric dimethylarginine (ADMA), which inhibits NO synthase…
View article: Metabolomic profiling of amines in sepsis predicts changes in NOS canonical pathways
Metabolomic profiling of amines in sepsis predicts changes in NOS canonical pathways Open
In early sepsis profound changes in amine levels were defined by dominant changes in the iNOS canonical pathway resulting in functionally meaningful changes in the ability of plasma to regulate iNOS activity ex vivo.
View article: The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice†
The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice† Open
Sepsis is the leading cause of direct maternal mortality, but there are no data directly comparing the response to sepsis in pregnant and nonpregnant (NP) individuals. This study uses a mouse model of sepsis to test the hypothesis that the…
View article: Dimethylarginine dimethylaminohydrolase 1 is involved in spinal nociceptive plasticity
Dimethylarginine dimethylaminohydrolase 1 is involved in spinal nociceptive plasticity Open
Activation of neuronal nitric oxide synthase, and consequent production of nitric oxide (NO), contributes to spinal hyperexcitability and enhanced pain sensation. All NOS isoforms are inhibited endogenously by asymmetric dimethylarginine, …
View article: Endothelial Dimethylarginine Dimethylaminohydrolase 1 Is an Important Regulator of Angiogenesis but Does Not Regulate Vascular Reactivity or Hemodynamic Homeostasis
Endothelial Dimethylarginine Dimethylaminohydrolase 1 Is an Important Regulator of Angiogenesis but Does Not Regulate Vascular Reactivity or Hemodynamic Homeostasis Open
Background— Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthesis and a risk factor for cardiovascular disease. Dimethylarginine dimethylaminohydrolase (DDAH) enzymes are responsible for ADMA breakdown. …
View article: Dimethylarginine Dimethylaminohydrolase 2 Regulates Nitric Oxide Synthesis and Hemodynamics and Determines Outcome in Polymicrobial Sepsis
Dimethylarginine Dimethylaminohydrolase 2 Regulates Nitric Oxide Synthesis and Hemodynamics and Determines Outcome in Polymicrobial Sepsis Open
Objective— Nitric oxide is a key to numerous physiological and pathophysiological processes. Nitric oxide production is regulated endogenously by 2 methylarginines, asymmetric dimethylarginine (ADMA) and monomethyl- l -arginine. The enzyme…