The Study Of The Correlation Between Coronary Artery Disease And Fractalkine And Its Receptor

BackgroundAtherosclerotic coronary artery disease (CAD) is a multifactorial process. Inflammation play a important role in the beginning and development of CAD. It is a critical step in inflammation that the activation and recruitment of mononuclear cells into the vessel wall. This step happens not only at the formation of the plaque, but also at the disruption of the plaque and the thrombokinesis. It is chemokine regulates the recruitment and infiltration of mononuclear cells.The family of chemokines is a series of cytokines that have the resemble structure and function. The molecular mass is about 8～12KD. Chemokines can be devide to four subgroup of CXC,CC,C and CX3C according to the location and function of the residua of aminothiopropionic acid. Fractalkine (FKN) is the only one of the CX3C subgroup. It has two existences: solubility pattern and membrane-binding pattern. CX3CR1 is the specific and high affinity receptor of FKN of people. It is expressed on monocytes, T lymphocytes and natural killer(NK) cells. FKN has a different character that integin-independence adhesive attraction by integrated with its receptor CX3CR1. Recently, some people have reported two common nonsynonymous single nucleotide polymorphisms of CX3CR1 that are in complete linkage disequilibrium (V249I and T280M). The expression of FKN was increased when the rejection of the cardiac transplantation of mice happened, but the procession with the CX3CR1 antibody prolonged significantly the survival time of the transplantation. This reflected the feature of the proinflammation cytokine of FKN. Some investigations indicated that FKN participated the injury of blood vessel by enhanced the adherence of endothelial cell and monocyte. The overexpression of FKN in artherosclerosis and the injury of blood vessel related intimately to the activation and adherence of the platelets. Therefore FKN could promote the thrombokinesis. In CX3CR1 gene-deficient mice, the recruitment of macrophages into the vessel wall were decreased obviously, atheromatous plaques were relieved distinctly. This showed us that FKN play a important role in the atheromatosis. Some reports showed that the 1249 allele of CX3CR1 could lower the morbid risk of CAD and improve endothelium-dependent vasodilation in white race. However, it was no relationship between polymorphism in CX3CR1 and ischemic cerebrovascular disease in Japanese people. We have no idea about the relationship between polymorphism in CX3CR1 and CAD in Han people, So the study of the relation and the protein expression of CX3CR1 becomes very significance.ObjectiveThe aim of this study was to evaluate the relationship between chemokine FKN, its receptor CX3CR1 and coronary artery disease (CAD) by searched the expression of CX3CR1 polymorphism in CAD, analyzed the protein expression of CX3CR1 in different alleles and measured the serum concentration of FKN.MethodsWe studied all 636 Hu Nan Han people subjects who visited in our hospital between 2005 and 2006. 326 persons were patients with CAD, the others were control. The diagnosis of CAD is corresponded to the diagnostic criteria of WHO in 1979. That who has the disease of organ transplantation, infection of HIV, kidney disease, other inflammations, tumors, wounded or operated within two weeks, serious liver or renal dysfunction, cerebral vascular accident within one month, disease of immune system and treated with immunomodulating drugs, taken medicine of Statin within one week before hospitalization.All the subjects were taken the peripheral blood, extracted DNA from the blood cells, surveyed the genetype with polymerase chain reaction (PCR). 130 of the subjects (90 patients and 40 controls) underwent cardiac catheterization. They were also taken the peripheral blood, drew off the monocytes, extracted the membrane protein, measured the quantity of the protein with western blot. Moreover, we detected the serum FKN with enzyme-linked immunosorbent assays.Results 1. The gene frequency distribution of V249I was significant difference between patients and controls (P＜0.05). The frequency of I249 allele in patients (0.160) was lower than that in controls (0.261), the odds ratios (OR) was 0.522, 95% confidence interval (CI) was 0.375～0.727. The frequency of M280 allele in patients (0.112) was lower than that in controls too, but it was no statistic meaning (P＞0.05).2. The relative optical density value of the protein of CX3CR1 in controls was lower than in stable angina and acute coronary syndrome (P＜0.05), and the acute coronary syndrome was more higher(P＜0.05).3. The relative optical density value of the protein of CX3CR1 in people with I249 allele (Ⅵ＋Ⅱ) was lower than that with genetypeⅤⅤ.4. The serum sFractalkine concentration in controls was lower than in stable angina and acute coronary syndrome (P＜0.05), and the acute coronary syndrome was more higher(P＜0.05).Conclusions1. The I249 allele is a protective gene for CAD2. CX3CR1 includes the pathogenic process of CAD and influences the stability of the atherosclerotic plaque.3. The I249 allele play a protection role by decreasing the expression of the protein of CX3CR1.4. The serum sFractalkine concentration in patients is high than in controls, and the acute coronary syndrome is the highest, so the level of serum sFractalkine may reflect the stability of the plaque.5. The level of serum sFractalkine can be a new predictive marker to judge whether coronary artery become stenosis or not.