Such expression can be detected even under normal condition or disease progression. Proteomics approach is very useful and powerful technology for detection and identification of protein expression in cells and biological samples (for recent review please see Larance and Lamond, 2015 Zhang et al., 2013). However, the underlying mechanisms of such consequences remain not fully understood. These include induction of oxidative stress at the blood-brain barrier (Dias et al., 2014), induction of angiogenesis and breast tumors (Pelton et al., 2014), induction of adipose dysfunction (Aguilar and Fernandez, 2014), accumulation of cholesterol in macrophages and other immune cells (Tall and Yvan-Charvet, 2015). Although, the hypercholesterolemia is asymptomatic, elevation of blood cholesterol for a long time leads to artherosclerosis and other pathological conditions. Data from World Health Organization (WHO, 2015) showed that mean value of blood cholesterol in Thailand of both genders was in a high range (5.1-5.6 mmol/L or 196.91-216.22 mg/dL) and prevalence of raised blood cholesterol was in between 50.0-59.9 % (WHO, 2015). The causes of hypercholesterolemia are associated with increased age, overweight, smoking, alcohol consumption, and family history (Cui et al., 2012 Le et al., 2006). Hypercholesterolemia, defined as high cholesterol levels in the blood, is one of the major risk factors for development and progression of artherosclerosis, cardiovascular diseases and stroke (Aguilar and Fernandez, 2014 Cui et al., 2012 Tracy and Tracy, 1997). Keywords: hypercholesterolemia, proteomics, retinol-binding protein, inflammation Introduction Among these differentially expressed proteins, the RBP4 has been proposed as a major linkage between hypercholesterolemia, adipose tissues, liver and kidney, which is believed to be a potential biomarker for metabolic and cardiovascular disorders associated with dyslipidemia in the future.
However, the mechanism of gelsolin reduction remains unclear. IL-6 and IL-1β), resulting in the synthesis of acute phase protein, in particular, haptoglobin and C-reactive proteins from hepatocytes. Such inflammation could further modulate the induction of cytokine release (e.g. The suppressing effect on RBP4 should be potentiated by the increase of complement factor B and CD5 antigen-like protein, which rendered the adipose tissues to overwhelm the liberation of RBP4 to blood circulation by metabolic and inflammatory processes. Moreover, the decrease of transthyretin might also be taken into accounts since it is known that the transthyretin usually forms complex with RBP4 to prevent glomerular filtration and excretion through the kidney. tumor necrosis factor α and interleukin-1β) from adipose tissues. Presumptive conclusion can be drawn that down-regulation of RBP4 might be attributable to the inflammation of adipocytes caused by the release of proinflammatory cytokines (e.g.
Confirmation by Western blotting revealed a significant reduction of RBP4 (approximately 50 %) in individual samples derived from the high group. Meanwhile, the other proteins such as haptoglobin, complement factor B and CD5 antigen-like protein were up-regulated upto +3.24, +1.96 and +2.04 fold, respectively. Results revealed that down-regulation of retinol-binding protein 4 (RBP4) (-2.26 fold), transthyretin (-1.25 fold) and gelsolin (-1.47 fold) was observed in the high group. Herein, using two-dimensional gel electrophoresis (2-DE) in conjunction with LC-MS searching has successfully been carried out to investigate the change of protein expression profiles as consequences of raised blood cholesterol at different levels (normal group: total cholesterol 200 mg/dL borderline high group: total cholesterol 200-239 mg/dL and high group: total cholesterol ≥ 240 mg/dL) (n = 45). Effects of hypercholesterolemia on alterations of serum proteins have not been fully elucidated.
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