Serum DPP4 Level In Patients With Coronary Artery Disease And Its Correlation With The Severity Of Coronary Artery Lesion

Objective: Coronary heart disease is short for coronary atherosclerotic heart disease, which is caused by coronary artery stenosis resulting in ischemia. Recent studies have demonstrated that atherosclerosis is a protective inflammation which is called Fiber proliferative response replying to local damage. If this damage continues for a period of time, this response will become excessive, eventually become a disease known as the plaque formation. In the process of plaque formation, lipid deposition is the most important factor and one of the manifestations to the damage. Both circulating hemameba and mononuclear are activated with the deposition of lipid and formation of the oxidized low-density lipoprotein cholesterol(ox LDL-C),the activated hemameba and mononuclear become foam cells by taking in ox LDL-C via scavenger receptor. With the necrosis of the foam cells, a lot of cholesterol ester will be released, along with the deposition of plasma lipoproteins, the cholesterol ester will be a plaque lipid core. With the development of inflammatory response, T cells activated, end to fibrogenesis, eventually form a fibrous cap.The risk of diabetes and CHD is the same. Except the hyperglycemia, diabetes also have the chronic inflammatory, oxidative stress, endothelial dysfunction and so on. Together with the hypertension and lipid metabolism disorder, is easy to cause cardiovascular disease and cardiovascular events.DPP4 is a 766-amino-acid and highly glycosylated Ⅱ transmembrane protein that belongs to a family of serine protease that cleave N-terminal dipeptides from proteins containing incretin hormones.The introduction of dipeptidyl peptidase 4(DPP4) inhibitors for the treatment of Type 2 diabetes acknowledges the fundamental importance of incretin hormones in the regulation of glycemia. Small molecule inhibitors of DPP4 exert their effects via inhibition of enzymatic degradation of glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic peptide(GIP). The widespread expression of DPP4 in tissues such as the vasculature and immune cells suggests that this protein may play a role in cardiovascular function. DPP4 is known to exert its effects via both enzymatic and non-enzymatic mechanisms. A soluble form of DPP4 lacking the cytoplasmic and transmembrane domain has also been recently recognized. Besides enzymatic inactivation of incretins, DPP4 also mediates degradation of many chemokines and neuropeptides. The non-enzymatic function of DPP4 plays a critical role in providing co-stimulatory signals to T cells via adenosine deaminase(ADA). DPP4 may also regulate inflammatory responses in innate immune cells such as monocytes and dendritic cells. The multiplicity of functions and targets suggests that DPP4 may play a distinct role aside from its effects on the incretin axis. Indeed recent studies in experimental models of atherosclerosis provide evidence for a robust effect for these drugs in attenuating inflammation and plaque development. Several prospective randomized controlled clinical trials in humans with established atherosclerosis are testing the effects of DPP4 inhibition on hard cardiovascular events.DPP4 not only plays an important role in the pathogenesis of type 2 diabetes, In non-diabetes, DPP4 can also lead to atherosclerosis through its proinflammatory role. Studies have confirmed that the activity of DPP4 plays an important role in forecasting onset and development of inflammation and atherosclerosis. But the activity of DPP4 is able to predict the degree of coronary artery lesions are rarely studied. This study aims to detect the DPP4 level in serum of coronary heart disease patients and with diabetes mellitus. Combined with coronary angiography results, explore the effects of DPP4 to coronary lesions in coronary heart disease patients. Seek new prediction method for severity of coronary artery lesion in patients with coronary artery disease.Methods:Contiguously selected patients, who underwent diagnosticcoronary angiography(CAG) at Vasculocardiology Deparment of The second affiliated hospital Of Hebei Medical University between May, 2014 and August, 2014, were enrolled in this prospective study. Inclusion criteria: preliminary diagnosed as coronary heart disease and agreed to undergo coronary angiography examination. exclusion criteria: Leukemia, multiple myeloma, anemia, thyroid disease, infectious diseases, acute or chronic kidney dysfunction, autoimmune disease and tumor. According to the results of coronary angiography and clinical history,Patients who’s Coronary artery were not seen obvious stenosis were classified to Coronary angiography negative groups. Angiographic CAD was defined as ≥ 50% luminal diameter stenosis of at least one of three epicardial coronary artery or left main coronary artery ≥ 30% luminal diameter stenosis. According to the 2014 ADA diabetes guidelines diagnosed with diabetes. The severity of CAD was determined using the SYNTAX score. Cubital vein blood samples were collected, after a 12-h fasting period in the morning the day after admission from all the subjects. 3000r/min centrifugal 10 min,-80℃save under test. Fasting plasma glucose(FPG), glycosylated hemoglobin(Hb Alc), triglycerides(TG), low-density lipoprotein cholesterol(LDLC),high-density lipoprotein cholesterol(HDLC) and other biochemical markers were measured by hospital clinical inspection Center automatic biochemical analyzer. Serum DPP4 levels were measured using ELISA. Kit were produced by Elabscience company, operation steps in strict accord with the kit instructions.Use SPSS 19.0 statistical software package for data statistics analysis,. measurement data must have normality test, Date which were normal distribution expressed by mean±standard deviation. Mean comparison between the two groups using t test. Mean comparison between groups using single factor analysis of variance, on the basis of the difference between groups, T test was used to compare between any two pairs. The normal distribution of variables were using linear correlation analysis of Pearson. Multivariate linear regression analysis was used to analyse influential factors, P<0.05 are statistically significant differences between them. Measurement data were expressed as a percentage, mean comparison between groups using χ2 test.Results: 1 96 patients were enrolled in this prospective study. Among the subjects, 63 had CHD [30 with DM(17 men and 13 women; mean age 60.50±6.87 years) and 33 without CAD(21 men and 12 women; mean age 53.7±9.2 years)], and 33 were Coronary artery negative(24 men and 9 women; mean age 60.27±6.82 years).2 No significant differences were found regarding Gender, age, smoking history and history of high blood pressure in three groups(P<0.05),Patients in CHD and CHD with DM groups had significantly higher BMI, LDL-C,CHOL, TG, hs-CRP levels than those of the control group(P<0.05). Patients in CHD with DM groups had significantly higher BMI, Hb Alc, GLU, hs-CRP, CHOL, TG levels than those of the CHD group(P<0.05). HDL-C levels were significantly lower in control group than those of the CHD and CHD with DM group, HDL-C levels were also lower in CHD group than those of the CHD with DM group.3 The difference was statistically significant in population mean of DPP4 in three groups of CHD(6.58±0.93), CHD with diabetes mellitus(11.10±1.51) and control group(3.29±0.57). the DPP4 Levels in CHD with DM group was higher than CHD group(T=-14.082, P=0.000), in CHD Group than control group(T=17.108, P=0.000).4 Serum DPP4 levels had a significant positive correlation with the Syntax score in CHD with diabetes mellitus group.(r=0.779;P=0.000).5 Serum DPP4 levels had a significant positive correlation with the Syntax score in CHD group(r=0.704;P=0.000).6 The Syntax score in CHD with DM group(23.98±4.14) was higher than CHD group(11.57±1.63)(T=-9626;P=0.000).7 Multiple linear regression showed that SYNTAX score has a linear regression relation with the concentration of DPP4, HDL-C, LDL-C, hs-CRP levels. By standardized regression coefficient, concentration of DPP4 Has the greatest impact on SYNTAX score.Conclusion: 1 DPP4 level were higher in CHD group than control group, in CHD with DM group will be higher.2 Serum DPP4 levels may become new prediction markers evaluating the severity of coronary artery lesion in CHD patients and provide scientific basis for looking for effective treatment.