<scp>ATP</scp> and arterial calcification

Fish, Richard S.; Klootwijk, Enriko; Tam, Frederick W.K.; Kleta, Robert; Wheeler, David C.; Unwin, Robert J.; Norman, J

doi:10.1111/eci.12055

Cited by 18 publications

(23 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is recent evidence for the involvement of CD73 in regulating arterial calcification, a pathological process characterized by calcium deposition in the intimal or medial layers of the vessel wall, which is associated with an increased risk of cardiovascular events [135,136]. In particular, a correlation between mutations of the NT5E gene, resulting in non-functional CD73, and the presence of symptomatic arterial and distal joint calcifications has been reported [137,138].…”

Section: Regulation Of Immunity By Cd39 and Cd73 In Atherosclerosis Amentioning

confidence: 99%

CD39 and CD73 in immunity and inflammation

Antonioli

Pacher

Vizi

et al. 2013

Trends in Molecular Medicine

1,007

933

View full text Add to dashboard Cite

The enzymatic activities of CD39 and CD73 play strategic roles in calibrating the duration, magnitude, and chemical nature of purinergic signals delivered to immune cells through the conversion of ADP/ATP to AMP and AMP to adenosine, respectively. This drives a shift from an ATP-driven proinflammatory environment to an anti-inflammatory milieu induced by adenosine. The CD39/CD73 pathway changes dynamically with the pathophysiological context in which it is embedded. It is becoming increasingly appreciated that altering this catabolic machinery can change the course or dictate the outcome of several pathophysiological events, such as AIDS, autoimmune diseases, infections, atherosclerosis, ischemia-reperfusion injury, and cancer, suggesting these ecto-enzymes are novel therapeutic targets for managing a variety of disorders.

show abstract

Section: Regulation Of Immunity By Cd39 and Cd73 In Atherosclerosis Amentioning

confidence: 99%

CD39 and CD73 in immunity and inflammation

Antonioli

Pacher

Vizi

et al. 2013

Trends in Molecular Medicine

1,007

933

View full text Add to dashboard Cite

show abstract

“…ATP binding enhanced the activity of ClC-5, the transporter mutated in Dent disease, a disease affecting the renal proximal tubule [405]. Arterial calcification is prevalent in patients with chronic kidney disease and ATP signalling appears to be involved (see review by [90]). …”

Section: Renal Injury and Failurementioning

confidence: 99%

Purinergic signalling in the kidney in health and disease

Burnstock

Evans

Bailey

2013

Purinergic Signalling

View full text Add to dashboard Cite

The involvement of purinergic signalling in kidney physiology and pathophysiology is rapidly gaining recognition and this is a comprehensive review of early and recent publications in the field. Purinergic signalling involvement is described in several important intrarenal regulatory mechanisms, including tuboglomerular feedback, the autoregulatory response of the glomerular and extraglomerular microcirculation and the control of renin release. Furthermore, purinergic signalling influences water and electrolyte transport in all segments of the renal tubule. Reports about purine-and pyrimidine-mediated actions in diseases of the kidney, including polycystic kidney disease, nephritis, diabetes, hypertension and nephrotoxicant injury are covered and possible purinergic therapeutic strategies discussed.

show abstract

“…Purinergic signalling plays a number of roles in the cardiovascular system (see review (Burnstock & Ralevic, 2014)). VSMCs express multiple P2 receptor subtypes (Wang et al, 2002) and, in recent years, several investigations have examined the role of purinergic signalling in the different forms of vascular calcification (Fish et al, 2013). However, they provide conflicting evidence as to whether extracellular nucleotides are harmful or protective.…”

mentioning

confidence: 99%

Inhibition of arterial medial calcification and bone mineralization by extracellular nucleotides: The same functional effect mediated by different cellular mechanisms

Patel

Zhu

Opdebeeck

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

Arterial medial calcification (AMC) is thought to share some outward similarities to skeletal mineralization and has been associated with the transdifferentiation of vascular smooth muscle cells (VSMCs) to an osteoblast-like phenotype. ATP and UTP have previously been shown to inhibit bone mineralization. This investigation compared the effects of extracellular nucleotides on calcification in VSMCs with those seen in osteoblasts. ATP, UTP and the ubiquitous mineralization inhibitor, pyrophosphate (PPi), dose dependently inhibited VSMC calcification by ≤85%. Culture of VSMCs in calcifying conditions was associated with an increase in apoptosis; treatment with ATP, UTP, and PPi reduced apoptosis to levels seen in non-calcifying cells. Extracellular nucleotides had no effect on osteoblast viability. Basal alkaline phosphatase (TNAP) activity was over 100-fold higher in osteoblasts than VSMCs. ATP and UTP reduced osteoblast TNAP activity (≤50%) but stimulated VSMC TNAP activity (≤88%). The effects of extracellular nucleotides on VSMC calcification, cell viability and TNAP activity were unchanged by deletion or inhibition of the P2Y2 receptor. Conversely, the actions of ATP/UTP on bone mineralization and TNAP activity were attenuated in osteoblasts lacking the P2Y2 receptor. Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) hydrolyses ATP and UTP to produce PPi. In both VSMCs and osteoblasts, deletion of NPP1 blunted the inhibitory effects of extracellular nucleotides suggesting involvement of P2 receptor independent pathways. Our results show that although the overall functional effect of extracellular nucleotides on AMC and bone mineralization is similar there are clear differences in the cellular mechanisms mediating these actions.

show abstract

ATP and arterial calcification

Cited by 18 publications

References 79 publications

CD39 and CD73 in immunity and inflammation

CD39 and CD73 in immunity and inflammation

Purinergic signalling in the kidney in health and disease

Inhibition of arterial medial calcification and bone mineralization by extracellular nucleotides: The same functional effect mediated by different cellular mechanisms

Contact Info

Product

Resources

About