The Expression Levels Of B7-H3 And B7-H4 Are Associated With The Severity Of Coronary Artery Lesions In Patients With Acute Coronary Syndrome

BACKGROUNDCoronary heart disease is a chronic disease. It causes great harm to human beings. The acute coronary syndrome (ACS) is the serious type of this disease. ACS is one of the most common causes of death among cardiovascular diseases. The pathological basis of the AS is the rupture of intimal plaques with secondary thrombosis. That results in coronary atherosclerosis, followed by coronary artery stenosis, spasms, and occlusion. Then a group of clinical syndromes such as myocardial ischemia and infarction will be caused. Lots of studies have shown that not only a large portion of lipids, but also invasions of inflammatory cells including monocytes and lymphocytes are found in AS plaques. Inflammatory reactions occur at almost every stage of development from fatty streaks to the advanced stage of atherosclerosis with complex lesions. In 1999, on the basis of damage theory, professor Ross put forward that "AS is an inflammatory disease". He believed that lipids and monocyte macrophages played key roles in the lesion formation process of AS.B7-H3 and B7-H4 are members of the superfamily B7 discovered recently. Currently, the mechanism of biological effects of B7-H3 remains controversial. The various immunological functions of B7-H3 may be related to different corresponding receptors. The research findings have shown that the serum level of B7-H3 is higher in patients with carotid atherosclerosis from the healthy controls. The significant increase in the serum level of B7-H3 after AMI is closely related to the occurrence of endpoint events. The correlation between the severities of coronary artery disease and B7-H3 has not been reported yet. B7-H4 (B7SI and B7x) are the youngest members of the B7 family. The mRNA expression of B7-H4 was found in lymphoid and non-lymphoid tissues and tumors. The expression of B7-H4 was found in activated human T cells, B cells, macrophages, and DCs. The studies on the relationship between B7-H4 and diseases are mostly confined to the autoimmune disease and tumors, but its relation to ACS has not been reported yet.OBJECTIVETo discuss the correlation between the severity of coronary artery disease and the variations of B7-H3 and B7-H4 and evaluate the diagnosis value of B7-H3 and B7-H4 through observing the levels of B7-H3 and B7-H4 (the novel soluble costimulatory molecules) of patients with different degrees of AS.METHODS182 patients with ACS and 68 normal controls were selected randomly. According to the results of coronary angiography, the 182 patients were divided into three groups, namely mild group (58 cases), moderate group (64 cases), and severe disease group (60 cases), based on the Gensini scores. The relative expression levels of mRNAs of B7-H3 and B7-H4 in PBMCs were measured by real-time fluorescent quantitative PCR; Levels of soluble B7-H3 and B7-H4 were detected by using an enzyme linked immunosorbent assay.RESULT1.The expression level of B7-H3 mRNA in PBMCs:Normal control group 1+0.42, Mild lesion group 1.13±0.28, Moderate lesion group 2.12±0.71, Severe lesion group 2.67±0.41 o There was no obvious difference in the expression level of B7-H3 mRNA between the mild disease group and the control group (P>0.05), while the level of B7-H3 mRNA in the severe disease group was the highest.It was significantly higher than that of the other three groups (P<0.01)2.The expression level of B7-H4 mRNA in PBMCs:Normal control group 1±0.62,Mild lesion group 0.94±0.35,Moderate lesion group 2.15 ±0.82,Severe lesion group 2.47±0.91。 Compared with the control group, the expression level of B7-H4 mRNA in mild disease group was slightly decreased (P>0.05).The level of B7-H4 mRNA in the severe disease group was the highest, significantly higher than that of the other three groups (P<0.01)3. The expression level of sB7-H3 in Peripheral blood:Normal control group 1813.46±346.96 pg/ml,Mild lesion group 2082.04± 409.64pg/ml,Moderate lesion group 2637.09±402.17pg/ml,Severe lesion group 4112.28±459.55pg/ml.The expression level of sB7-H3 increased gradually with the gradual aggravation of the coronary disease. The level of sB7-H3 in the severe disease group was the highest.It was significantly higher than that of the other three groups (P<0.01)4.The expression level of sB7-H4 in Peripheral blood:Normal control group 2245.6±362.84 pg/ml,Mild lesion group 2163.04±409.71pg/ml,Moderate lesion group 2768.09±396.24pg/ml,Severe lesion group 4235.28± 503.93pg/ml.Compared with the control, the expression level of sB7-H4 in mild disease group was slightly decreased(P>0.05).The level of sB7-H4 in the severe disease group was the highest, significantly higher than that of the other three groups (P<0.01)5. A positive correlation was found between the level of sB7-H3 in Peripheral blood and the corresponding Gensini scores:r=0.632, P<0.01.A positive correlation was found between the level of sB7-H4 in Peripheral blood and the corresponding Gensini scores:r=0.538, P<0.01.6. Serum sB7-H3 and sB7-H4 level is closely connected with the risk degree of coronary heart disease, therefore, is a factor of the aggravation of the risk degree of ACS.A positive correlation was found between the level of sB7-H3 in Peripheral blood and the corresponding Grace scores:r=0.478, P< 0.01.A positive correlation was found between the level of sB7-H4 in Peripheral blood and the corresponding Grace scores:r=0.43, P<0.01.CONCLUSIONThe levels of B7-H3 and B7-H4 in Peripheral blood gradually increased with the gradual aggravation of the severity of coronary artery lesions. A positive correlation was found between the level of both sB7-H3 and sB7-H4 in Peripheral blood and the corresponding Gensini scores.A positive correlation was found between the level of both sB7-H3 and sB7-H4 in Peripheral blood and the corresponding Grace scores.Serum sB7-H3 and sB7-H4 level is closely connected with the risk degree of coronary heart disease, therefore, is a factor of the aggravation of the risk degree of ACS.The levels of both sB7-H3 and sB7-H4 could be used as important biomarkers for atherosclerosis in clinical practice, and be of practical values in the diagnosis and assessment of coronary atherosclerosis.