The kinetics of hyaluronan in normal and acutely inflamed synovial joints: Observations with experimental arthritis in sheep

Background: Rheumatoid arthritis (RA) induces systemic inflammation, producing a range of co-morbidities including cardiovascular disease. An early vascular change is endothelial dysfunction, characterized by reduced endothelium-dependent vasodilation. The aim of this study was to assess endothelial function in isolated coronary and digital arteries using an ovine model of collagen-induced RA. Methods: Sheep were culled following induction of arthritis, and their endothelial function was compared to that of normal sheep. Paired arterial segments were mounted in a wire myograph and dilated with endothelium-dependent vasodilators [bradykinin, serotonin, carbachol and adenosine diphosphate (ADP); linked to either Gi or Gq signalling pathways] and endothelium-independent dilators (adenosine and sodium nitroprusside) to construct cumulative concentration-response curves. Results: Coronary arteries from arthritic sheep exhibited a significantly greater EC₅₀ value for bradykinin-induced relaxation compared to non-arthritic controls (2.9 × 10^-8M for arthritic sheep vs. 8.6 × 10^-9M for controls). Digital arteries from arthritic sheep also exhibited a significantly greater EC₅₀ for relaxation to ADP and a significant decrease in the carbachol maximal response. Responses to sodium nitroprusside were unchanged in both coronary and digital arteries. Conclusion: Sheep with RA demonstrated attenuated arterial relaxation to endothelium-dependent vasodilators. This may provide a useful model of endothelial dysfunction in chronic inflammatory conditions. The dysfunction did not appear to be associated with one specific G-protein signalling pathway.

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“…This model has previously been reported to induce pathology similar to that seen in RA [35,36]. Arthritis was induced using a 6-week protocol.…”

Section: Methodsmentioning

confidence: 99%

Endothelial Dysfunction in an Ovine Model of Collagen-Induced Arthritis

Dooley

Washington²,

Abdalmula³

et al. 2014

J Vasc Res

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“…A constant flow of HA occurs through the normal joint, with a half-life of 12 hours in rabbits and 1 day in sheep (13,14). Although it has been reported that synovial fluid flow is diminished in osteoarthritis (OA) (2), most measurements indicate more rapid clearance of both HA and protein from joints with synovitis, even when it is as mild as that commonly seen in OA (15,16).…”

Section: Introductionmentioning

confidence: 99%

Intraarticular injection of hyaluronan as treatment for knee osteoarthritis: What is the evidence?

Brandt

Smith

Simon

2000

Arthritis & Rheumatism

178

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“…While this rationale was soundly based, the short half-life (< 24 h) of HA when injected into knee joints [4,5] was inconsistent with the observed clinical effects of HA which were reported to last for several weeks or even months after intra-articular (i. a.)…”

Section: Introductionmentioning

confidence: 99%

Hyaluronan molecular weight and polydispersity in some commercial intra-articular injectable preparations and in synovial fluid

Adam¹,

Ghosh²

2001

Inflamm. res.

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Seven commercially available hyaluronan preparations of reported molecular weight were analysed. The weight average molecular weight (Mw) and number average molecular weight (Mn) values obtained for 6 of the 7 preparations using the MALLS-GPC system were in good agreement with the reported values. The abnormally low values for the exception suggested that degradation of hyaluronan had occurred. The MALLS-GPC technique was then used to determine the molecular characteristics of the endogenous hyaluronan in normal ovine synovial fluids. While the Mws ranged from less than 1 x 10(6) Da to 7 x 10(6) Da the majority were between 1-3 x 10(6) Da. [mean Mw = 2.42 x 10(6), mean Mn = 2.21 x 10(6) Da]. The effects of freezing and thawing synovial fluid upon molecular weight of hyaluronan were also investigated and were found to diminish both Mz and Mw values.

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The kinetics of hyaluronan in normal and acutely inflamed synovial joints: Observations with experimental arthritis in sheep

Cited by 105 publications

References 17 publications

Endothelial Dysfunction in an Ovine Model of Collagen-Induced Arthritis

Endothelial Dysfunction in an Ovine Model of Collagen-Induced Arthritis

Intraarticular injection of hyaluronan as treatment for knee osteoarthritis: What is the evidence?

Hyaluronan molecular weight and polydispersity in some commercial intra-articular injectable preparations and in synovial fluid

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