Role Of C-reactive Protein In Metabolic Syndrome

Background and objectives: Metabolic syndrome (MS) is a clustering character of multifactorial cardiovascular risk. Many reports showed that MS is a low-grade, systemic, inflammatory condition, of which inflammation maybe play a pivotal role. As a sensitive marker of inflammation, CRP was more significantly associated with MS. It was confirmed that the basal level of CRP could accurately predict the risk of the occurrence of heart diseases, stroke, sudden cardiac death, and the development of peripheral arterial disease. The purposes of this study were to determine the association of hs-CRP and components and target organ damage in patients with MS, to identify elevated CRP levels as one of the risk factors of MS, and to investigate the change of CRP in cardiovascular and adipose tissues in rats with MS. Methods: 1. Clinical study: A total of 801 participants were included in this study. MS criteria was defined by modified NCEP-ATP III. Serum hs-CRP, fasting blood lipids and glucose, blood pressure, waist circumference, TG, HDL-C, LDL-C, UAER, IMT and LVMI were measured in all the participants. Moreover, we also investigated CRP gene 1059G/C polymorphism by PCR-RFLP. 2. Experimental study: Male Wistar rats were fed with 45% fat, 2% salt and other ingredients, while control rat fed with 10% fat and 0.5% salt for 52 weeks. Rat tail pressure, heart rate, body weight and blood glucose were measured regularly. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic glucose clamp technique. CRP protein and CRP mRNA expression were assessed by Western blot analysis and RT-PCR analysis, respectively. Results: 1. Clinical study (1) Increasing numbers of the MS components resulted in higher serum levels of hs-CRP. (2) Highly positive correlation between the serum concentration of hs-CRP and waist circumference, BP, FPG, TG were observed, and significant negative correlation between serum level of hs-CRP and HDL-C was found. (4) A receiver operating characteristic (ROC) curve was performed to evaluate the sensitivity and specificity of hs-CRP for MS diagnosis, and presented an area under the curve (AUC) of 0.72. A significant positive correlation between hs-CRP and IMT, LVMI and UAER was also confirmed. (5) Levels of the serum hs-CRP, SBP, waist circumference and FPG were significantly lower in participants with GC genotype as compared with GG genotype in CRP 1059G/C gene polymorphism. 2. Experimental study: (1) Compared with control group, MS rats had abdominal obesity, high TG, fasting blood glucose, high blood pressure and severe insulin resistance, which resembled with clinical characteristics of human MS. MS rats had hypertrophy, visceral and brown fat hypertrophy. Heart, blood vessel, and kidney function damage was more severe and occurred more frequently in rats with MS. (2) The mRNA and protein expression of CRP in left ventricular, visceral and brown adipose tissue were significantly up-regulated in rats with MS compared with control rats. However, both mRNA and protein expressions of CRP in aorta were unchanged compared with control rats. Conclusions: 1. The higher hs-CRP concentration was closely correlated with MS and its target organ damage. The elevated hs-CRP level could be a new risk factor for MS. 2. The CRP gene 1059 GG genotype may be one of the contributors for the increased susceptibility to MS. 3. Increased expression of CRP may be involved in the cardiac hypertrophy and obesity in rats with MS.