Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells

Herbrig, Kay; Haensel, Sven; Oelschlaegel, Uta; Pistrosch, Frank; Foerster, Sarah; Passauer, Jens

doi:10.1136/ard.2005.035378

Cited by 137 publications

(150 citation statements)

References 23 publications

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“…In contrast to the above-mentioned observations of elevated circulating EPC levels in mouse arthritis models, studies in humans have shown that EPCs are decreased in the peripheral blood of patients with active RA compared with healthy individuals (21,22). Depletion of EPCs from the circulation in RA patients with established disease reflects their enhanced extravasation out of the bloodstream and into the inflamed joint.…”

Section: Discussionmentioning

confidence: 86%

The role of vascular cell adhesion molecule 1/ very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium

Silverman¹,

Haas²,

Rad³

et al. 2007

Arthritis & Rheumatism

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Objective. Marrow-derived endothelial progenitor cells (EPCs) are important in the neovascularization that occurs in diverse conditions such as cardiovascular disorders, inflammatory diseases, and neoplasms. In rheumatoid arthritis (RA), synovial neovascularization propels disease by nourishing the inflamed and hyperproliferative synovium. This study was undertaken to investigate the hypothesis that EPCs selectively home to inflamed joint tissue and may perpetuate synovial neovascularization.Methods. In a collagen-induced arthritis (CIA) model, neovascularization and EPC accumulation in mouse ankle synovium was measured. In an antibodyinduced arthritis model, EPC recruitment to inflamed synovium was evaluated. In a chimeric SCID mouse/ human synovial tissue (ST) model, mice were engrafted subcutaneously with human ST, and EPC homing to grafts was assessed 2 days later. EPC adhesion to RA fibroblasts and RA ST was evaluated in vitro.Results. In mice with CIA, cells bearing EPC markers were significantly increased in peripheral blood and accumulated in inflamed synovial pannus. EPCs were 4-fold more numerous in inflamed synovium from mice with anti-type II collagen antibody-induced arthritis versus controls. In SCID mice, EPC homing to RA ST was 3-fold greater than to normal synovium. Antibody neutralization of vascular cell adhesion molecule 1 (VCAM-1) and its ligand component ␣4 integrin potently inhibited EPC adhesion to RA fibroblasts and RA ST cryosections.Conclusion. These data demonstrate the selective recruitment of EPCs to inflamed joint tissue. The VCAM-1/very late activation antigen 4 adhesive system critically mediates EPC adhesion to cultured RA fibroblasts and to RA ST cryosections. These findings provide evidence of a possible role of EPCs in the synovial neovascularization that is critical to RA pathogenesis.

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Section: Discussionmentioning

confidence: 86%

The role of vascular cell adhesion molecule 1/ very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium

Silverman¹,

Haas²,

Rad³

et al. 2007

Arthritis & Rheumatism

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“…36 In addition, adhesion to mature endothelial cells after activation with TNF-␣ was enhanced only in controls but not in patients with rheumatoid arthritis. 37 The functional activities of isolated EPCs, such as proliferative, migratory, adhesive, and in vitro vasculogenesis capacity, were also impaired in patients with hypercholesterolemia. 38 Finally, in SHR as well as in patients with essential hypertension endothelial function is impaired and may contribute to reduced vessel regeneration in this setting.…”

Section: Discussionmentioning

confidence: 99%

Hypertension Impairs Postnatal Vasculogenesis

et al. 2008

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Key Words: hypertension Ⅲ angiogenesis Ⅲ progenitor cells Ⅲ angiotensin converting enzyme Ⅲ angiotensin type I receptor T he revascularization process, including vasculogenesis, angiogenesis, and collateral growth, characterizes tissue repair and remodeling occurring in acute and chronic ischemic vascular diseases. In particular, postnatal vasculogenesis referred to the homing and differentiation of circulating progenitor cells from bone marrow or non-bone marrow origins 1 into endothelial cells within sites of active neovascularization. In addition, circulating progenitor cells may deliver angiogenic growth factors to pathological tissues and contribute to neovascularization and tissue/vessel remodeling by paracrine effects. 2,3 In most clinical settings, however, these natural adaptive responses to a compromised perfusion are insufficient to block the progression of ischemic diseases. Hence, certain cardiovascular risk factors including diabetes, aging, and hypercholesterolemia adversely affect postnatal vasculogenesis and revascularization in animals models of limb ischemia. 4 -7 In support of this view, patients with type I and II diabetes displayed a reduction in endothelial progenitor cell (EPC) number and angiogenicity. 8,9 In most forms of clinical and experimental hypertension, increased arterial blood pressure is associated with microvascular rarefaction and increased peripheral vascular resistances. 10 Similarly, postischemic reparative neovascularization is impaired in spontaneously hypertensive rats (SHR) as a function of progression of the hypertensive disease. 11,12 Several molecular and cellular mechanisms may be involved in the hypertension-induced impairment in vessel growth. First, the angiogenic capacity of serum derived from SHR was less than that from normotensive animals in a chick embryo chorio-allantoic membrane model. 13 Protein levels of key proangiogenic growth factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor are also reduced in hypertensive animals. 11,14 Second, previous obser-

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“…Like other cardiovascular risk factors, RA is associated with endothelial dysfunction (Herbrig, Haensel et al 2006). Patients with RA have a life expectancy that is reduced by 5-10 years and the excess mortality is from cardiovascular disease which is increased roughly 4-fold (Wrigley, Lip et al 2010).…”

Section: Inflammatory Conditionsmentioning

confidence: 99%

“…However, the patients with RA that are at particular cardiovascular risk are those with active disease and high disease activity scores (Grisar, Aletaha et al 2005). EPC numbers and EPC proliferative capacity show an inverse correlation with disease activity scores (Grisar, Aletaha et al 2005;Herbrig, Haensel et al 2006;Egan, Caporali et al 2008). The increased risk of cardiovascular events is not limited to RA and has been described in other inflammatory states such as systemic lupus erythematosus (SLE) (Urowitz, Bookman et al 1976;Roman, Shanker et al 2003), human immunodeficiency virus (HIV) infection (van Leuven, Sankatsing et al 2007), inflammatory bowel disease (Danese and Fiocchi 2003) or periodontitis (Mattila, Nieminen et al 1989).…”

Section: Inflammatory Conditionsmentioning

confidence: 99%

Endothelial Progenitor Cell Number: A Convergence of Cardiovascular Risk Factors

Hoenig¹,

Sellke²

2012

Cardiovascular Risk Factors

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Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells

Cited by 137 publications

References 23 publications

The role of vascular cell adhesion molecule 1/ very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium

The role of vascular cell adhesion molecule 1/ very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium

Hypertension Impairs Postnatal Vasculogenesis

Endothelial Progenitor Cell Number: A Convergence of Cardiovascular Risk Factors

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