Osteopontin Is Associated with Increased Arterial Stiffness in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) patients are characterized by increased arterial stiffness, an independent predictor of cardiovascular risk. It has been suggested that osteopontin (OPN), a cytokine involved in RA pathogenesis, might have vascular effects. To study a possible relationship between OPN and arterial stiffness, aortic pulse wave velocity (PWV) was measured by tonometry in 69 patients (41 with RA, 28 with systemic sclerosis [SSc]) and 18 healthy controls. Plasma OPN levels, oxidative stress markers, and endothelin 1 (ET-1) were assessed. OPN levels were significantly (P < 0.05) higher in RA (median 9.93, range 4.36-47.80 ng/mL) than in SSc (4.3, 2.1-19.7 ng/mL) or controls (5.2, 4.1-9.4 ng/mL). In RA patients, log-OPN was related to log-C-reactive protein (log-CRP) (r = 0.30, P < 0.05), age (r = 0.38, P < 0.01), Health Assessment Questionnaire (HAQ) (r = 0.58, P < 0.0001), and inversely related to total cholesterol (r = -0.33, P < 0.05) and apolipoprotein A (apoA) (r = -0.58, P < 0.001), but not to oxidative stress markers and ET-1. PWV was similar in RA (median 8.1, range 4.7-16.4 m/s) and SSc (median 8.7, range 7.1-13.1 m/s), but significantly greater (P < 0.01) than controls (median 7.5, range 4.1-10.4 m/s). Aortic PWV was related to log-OPN (r = 0.40, P < 0.01) only in RA patients. It also was related to age (r = 0.34, P < 0.05), mean blood pressure (r = 0.44, P < 0.001), and HAQ (r = 0.48, P < 0.001). In multiple regression analysis (r 2 = 0.36), including confounders, log-OPN remained a significant predictor (P < 0.05) of PWV in RA. Elevated plasma OPN levels are associated with increased arterial stiffness in RA patients, suggesting that this protein might represent a bridge protein between inflammation and the consequent joint damage and cardiovascular risk in RA patients.

Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile

“…In agreement with the results obtained in our study, circulating OPN levels were also associated with a dysmetabolic profile in other autoimmune diseases, such as psoriasis and rheumatoid arthritis (22,31); in these cohorts, higher OPN concentrations correlated with hypertension and increased arterial stiffness. The hypothesis of a direct role of OPN in atherosclerosis is supported by the occurrence of more severe cardiovascular disease and restenosis after percutaneous coronary intervention in patients with elevated OPN levels, independent of traditional cardiovascular risk factors (32,33).…”

Serum osteopontin negatively impacts on intima‐media thickness in patients with systemic lupus erythematosus

“…Due to the small sample size and the absence of previous studies investigating the subset of patients with SLE, the results concerning the primary outcome should be considered as part of “pilot” study. Nevertheless, the sample size is in line with previous studies investigating the relationship between OPN and cIMT in other autoimmune systemic inflammatory diseases …”

“…Due to the small sample size of this cohort, a result overestimation has to be carefully considered and no definite conclusions can be stated. However, our cohort was already validated and the sample size is in line with previous studies . Similarly, the ultrasonography method to measure cIMT has been widely published and known to be partially dependent on the operator and the methods .…”

“…Nevertheless, the sample size is in line with previous studies investigating the relationship between OPN and cIMT in other autoimmune systemic inflammatory diseases. [17][18][19]…”

Osteopontin and integrin are involved in cholesterol gallstone formation

“…Osteopontin (OPN) is an acidic extracellular matrix glycoprotein present in several human organs and body fluids [10–13]. It possesses a characteristic RGD (Arg-Gly-Asp) sequence and the calcium binding property [14] and exerts many of its biological effects by interacting with integrins [15].…”