Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity, insulin resistance, diabetes, dyslipidemia, and atherosclerosis. The complement system was originally viewed as a supportive first line of defense against microbial invaders, and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes, involving in such diverse processes as clearance of the immune complexes, complementing T and B cell immune functions, tissue regeneration, and metabolism. The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity, insulin resistance and diabetes mellitus. In addition, we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy, nephropathy and neuropathy, highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.

• Inflammation
• Complement activation
• Metabolic disorders
• Obesity
• Insulin resistance
• Type 2 diabetic mellitus

• Adolescent
• Apolipoprotein A-I/blood
• Biomarkers/blood
• Case-Control Studies
• Child
• Child, Preschool
• Female
• Haptoglobins/metabolism
• Hepatitis B, Chronic/blood
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/pathology
• Humans
• Male
• Predictive Value of Tests
• ROC Curve
• alpha-Macroglobulins/metabolism

AIM: To find out the relationship between the gene transcription of different types of procollagen and the deposition of the relevant collagens in the liver tissue and to confirm the types of collagen producing cells in liver fibrogenesis.

METHODS: Dynamic changes of the expression of α1(I), α1(III) and α1(IV) procollagen mRNA and relevant collagens and the distribution of collagen producing cells during liver fibrogenesis of rat induced by CCl₄ (20 weeks) were investigated with Northern blot analysis, in situ hybridization and immunohistochemical techniques.

RESULTS: The increased expression of α₁(III) procollagen mRNA by Northern blot analysis was the most predominant one among the three mRNAs during fibrogenesis. However, the enhanced expression of α₁(IV) procollagen mRNA occurred very early while the expression of α1(I) mRNA was not enhanced much until the middle stage of the experiment. Desmin (Dm) positive hepatic stellate cells (HSCs) and few myofibroblasts (MFs) in and around the necrotic areas expressed α1(I), α1(III) and α1(IV) procollagen mRNA signals detected by in situ hybridization at the early stage of the experiment. All the three procollagen mRNA signals thereafter mainly localized in fibroblasts (Fbs) and MFs in fibrotic septa during the middle and late stages of fibrosis, which distributed parallel to the corresponding collagens detected by immunohistochemical study. In addition, the endothelial cells of sinusoids and the small blood vessels within the septa also showed α1(IV) procollagen mRNA and type IV collagen expression

CONCLUSION: It is considered that “HSC-MF-Fb” effect cell system is the major cellular source of collagen production in liver fibrosis, in which HSCs are collagen producing precursor cells in the early liver fibrogenesis, thereafter the synthesis of type I, III and IV collagens (Col I, Col III and Col IV) mainly derives from MFs and Fbs, which play a very important role in the progress of liver fibrosis. The endothelial cells along sinusoids, as another source of Col IV production, might participate in the capillization of liver sinusoids.

• Procollagen mRNA
• immunohistochemistry
• Northern blot analysis
• in situ hybridization
• liver fibrosis

AIM: To determine whether serum vascular endothelial growth factor (VEGF) levels correlates with the severity of liver cirrhosis and whether portal hypertension impacts on the expression of serum VEGF protein.

METHODS: Fifty-three patients (mean age 56 ± 2 years) with HCV (n = 26), HBV (n = 13), and cryptogenic liver cirrhosis (n = 14) (Child-Pugh-s class A: 24, B: 19 and C: 12) and normal renal function constitute the patient population, who were all diagnosed by clinical, histological and radiological findings. Six healthy people and six patients with acute hepatitis served as controls. Severity of liver disease was evaluated by the CP score. Serum levels of IGF-1 and VEGF were measured by radioimmunoassay and ELISA, respectively. Portal hypertension was assessed using pulsed Doppler ultrasound.

RESULTS: The mean serum VEGF levels in all cirrhotic patients (73 ± 58) were significantly lower than those of healthy controls (360 ± 217, P < 0.01) and acute hepatitis (1123 ± 1261, P < 0.01) respectively. No significant difference in median serum VEGF levels were noted among the different Child-Pugh-s classes (class A: median, 49.4 ng/L, range, 21-260 ng/L, Class B: median 59.9 ng/L; range 21-92, and Class C: median 69; range 20-247 ng/L). A significant correlation was noted between serum VEGF and two accurate parameters of portal hypertension: portal blood flow velocity (r = 06) and spleen size (r = 0.55). No correlation was found between VEGF serum levels and serum albumin, IGF-1, platelets count and aminotrasnferases (r = 0.2, r = 0.1, r = 0.2 and r = 0.2, respectively).

CONCLUSION: Circulating VEGF level in patients with liver cirrhosis could not serve as an indicator of the progression of chronic liver disease but rather, they may reflect increased portal hypertension or decreased hepatic regenerative activity or the combination of both.

• VEGF
• growth factors
• liver cirrhosis
• liver regeneration
• hypertension portal
• duplex sonography
• angiogenesis