Objective This work studied the presence of inflammatory and atherogenic lipoprotein markers that could explain the high incidence of cardiovascular disease (CVD) reported in rheumatoid arthritis (RA) patients. Methods Inflammatory markers were 1) soluble adhesion molecules (intercellular adhesion molecule [ICAM] and vascular cell adhesion molecule [VCAM]), 2) C‐reactive protein (CRP), 3) fibrinogen (Fb), 4) cytokines (interferon‐γ [IFNγ], tumor necrosis factor α [TNFα]), and 5) secretory group IIA phospholipase A₂(sPLA₂‐IIA). Atherogenic lipoprotein markers were 1) the size distribution of plasma lipoprotein subclasses, and 2) the binding affinity of low‐density lipoprotein (LDL) to chondroitin 6‐sulfate glycosaminoglycan (GAG). Results RA patients (n = 31) and matched controls (n = 28) had similar plasma concentrations of total cholesterol, triglycerides, Apo B, Apo A‐I, very low‐density lipoprotein, intermediate‐density lipoprotein, and high‐density lipoprotein (HDL). RA patients had significantly higher plasma levels of sPLA₂‐IIA, ICAM, CRP, Fb, TNFα, and IFNγ compared with controls. RA patients also had significantly higher levels of small, dense LDL‐1 (P < 0.05) and lower levels of small HDL‐2 particles (P < 0.001) compared with controls. In addition, LDL from RA patients had a significantly higher binding affinity (K_d) to GAG (mean ± SD K_d 204 ± 22.4 nM Apo B) than did LDL from control subjects (K_d 312 ± 36 nM Apo B) (P < 0.05). This K_d value showed a significant negative correlation with the plasma levels of LDL‐1 (r = −0.566, P ≤ 0.004). In RA patients, a significant positive correlation was obtained between sPLA₂‐IIA and CRP, ICAM, and LDL‐1. HDL‐2 showed a negative correlation with sPLA₂‐IIA. Conclusion These atherogenic lipoprotein factors combined with the presence of chronic inflammation may contribute to the high CVD‐related mortality in RA patients.

Several studies suggest that variations in the concentration of plasma glycoproteins can influence cellular changes in a large number of diseases. In recent years, proton nuclear magnetic resonance (¹H-NMR) has played a major role as an analytical tool for serum and plasma samples. In recent years, there is an increasing interest in the characterization of glycoproteins through ¹H-NMR in order to search for reliable and robust biomarkers of disease. The objective of this review was to examine the existing studies in the literature related to the study of glycoproteins from an analytical and clinical point of view. There are currently several techniques to characterize circulating glycoproteins in serum or plasma, but in this review, we focus on ¹H-NMR due to its great robustness and recent interest in its translation to the clinical setting. In fact, there is already a marker in H-NMR representing the acetyl groups of the glycoproteins, GlycA, which has been increasingly studied in clinical studies. A broad search of the literature was performed showing a general consensus that GlycA is a robust marker of systemic inflammation. The results also suggested that GlycA better captures systemic inflammation even more than C-reactive protein (CRP), a widely used classical inflammatory marker. The applications reviewed here demonstrated that GlycA was potentially a key biomarker in a wide range of diseases such as cancer, metabolic diseases, cardiovascular risk, and chronic inflammatory diseases among others. The profiling of glycoproteins through ¹H-NMR launches an encouraging new paradigm for its future incorporation in clinical diagnosis.

Background: Glucose-regulated protein 78/Binding immunoglobulin protein (GRP78/BiP) is a protein associated with endoplasmic reticulum stress and is upregulated by metabolic alterations at the tissue-level, such as hypoxia or glucose deprivation, and it is hyper-expressed in fat tissue of obese individuals. Objective: To investigate the role of the GRP78/BiP level as a metabolic and vascular disease biomarker in patients with type 2 diabetes (DM), obesity and metabolic syndrome (MS). Methods: Four hundred and five patients were recruited, of whom 52.5% were obese, 72.8% had DM, and 78.6% had MS. The intimae media thickness (cIMT) was assessed by ultrasonography. The plasma GRP78/BiP concentration was determined, and its association with metabolic and vascular parameters was assessed. Circulating GRP78/BiP was also prospectively measured in 30 DM patients before and after fenofibrate/niacin treatment and 30 healthy controls. Results: In the cross-sectional study, the GRP78/BiP level was significantly higher in the patients with obesity, DM, and MS. Age-, gender- and BMI-adjusted GRP78/BiP was directly associated with LDL-cholesterol, non-HDL-cholesterol, triglycerides, apoB, and cIMT. GRP78/BiP was positively associated to carotid plaque presence in the adjusted model, irrespective of obesity, DM and MS. In the prospective study, nicotinic acid treatment produced a significant reduction in the GRP78/BiP levels that was not observed with fenofibrate. Conclusions: GRP78/BiP plasma concentrations are increased in patients with both metabolic derangements and subclinical atherosclerosis. GRP78/BiP could be a useful marker of metabolic and cardiovascular risk.