| Background Epicardial adipose tissue(EAT)is a risk marker for metabolic syndrome and cardiovascular disease and is anatomically very close to the adventitia of the coronary circulatory system and the myocardium.EAT is made up of fat cells, as well as lymphocytes,macrophages and mast cells.It is now widely accepted that EAT inflammation is involved in the development of atherosclerosis. Clinical research has also confirmed the association between EAT and coronary heart disease (CHD), with the effect of EAT’s cellular and molecular mechanisms on CHD becoming increasingly apparent. Recent studies have postulated that the pathogenesis of CHD may be from "outside to inside" rather than the traditional model, in which endothelial tissue is damaged by intravascular conditions, such as hypertension, hyperlipemia and hyperglycemia, leading to dysfunction of the endothelium, intimal hyperplasia and the formation of lipid core coronary plaques. Neovascularization/vasa vasorum neovascularization and vascular-remodeling are significant influences in the progression and composition of vulnerable coronary plaque.In the early stages of atherosclerotic lesions in coronary arteries, intimal thickening causes smooth muscle cells (SMC) to secrete hypoxia-inducible factor (HIF).HIF and other inflammatory cytokines (such as TNF-a) can induce neointimal thickness and fatty streaks in the vasa vasorum. New evidence has recently suggested that inflammatory HIFs are secreted by EAT involved in the process of angiogenesis.Angiogenesis or neovascularizationcanreduce the effect of hypoxia on intimal thickening in the early stages of coronary atherosclerotic lesions. Vasa vasorum can, however, transferharmful inflammatory cytokines and adipocytokines derived from EAT into the neointima and fatty plaque; this can increase neointimal inflammation and plaque formation. Some studies have suggested that cytokines and adipocytokines derived from EAT can increase lymphocyte, macrophage and mast cell activity around perivascular adipose tissue. Furthermore, macrophages migrating into plaque via the vasa vasorum and surrounding perivascular adipose tissue become a source of foam cells, playing a role in the pathogenesis of atherosclerosis. Macrophages are a major source of metalloproteinases (MPs), and there is evidence that the secretion of MPs in EAT is higher in patients with CHD than non-coronary heart disease. The matrix metalloproteinase(MMP) system plays a key role in the degradation of extracellular matrix (ECM) components, while smooth muscle cell migration and infiltration of macrophages is important for neointimal formation after vascular injury.Degradation of ECM, hemodynamic stimuli,elastolysis and collagenolysis leads to significant migration of smooth muscle cells, contributing to lasting structural changes in the vascular wall (vascular remodeling)during the progression of cardiovascular disease. Other evidence demonstrates that the rate of fatty acid release by EAT is approximately twice that of the pericardial and peri-renal tissue depots. High levels of epicardial fatty acids can cause the accumulation of lipids in plaque.In the present study, increased EAT was significantly related to Intravascular Unltrasound(IVUS)parameters that indicated vulnerable plaque such as an increased lipid core size and greater manifestation of thin-cap fibroatheroma (TCFAs). Current evidence demonstrates that intensive cholesterol-lowering therapy using statins reduces EATV.Recent evidence shows that epicardial adipose not only participate in the development of the occurrence of arterial sclerosis in inflammation, it is representative heart the reliability index of the metabolic abnormalities associated with patients’blood pressure level, blood pressure circadian rhythm, and epicardial fat present a certain age and gender differences,These problems is a lack of in-depth research at home and abroad, based on the above evidence, we used DSCT measureing epicardial adipose and discussed the relationship between epicardial adipose and cardiovscular traditional risk factors and the coronary atherosclerosis plaque vulnerability from clinical to basic experiment by using quantitative imaging methods of coronary CTA and molecular biological technique.Objective1 This article will investigate the relation of epicardial adipose tissue volume (EATV) determined by dual-source CT (DSCT) cardiac angiography of levels and circadian rhythm of blood pressure.2 To investigate the effect of the differences of age and gender on the association between epicardial adipose tissue volume and coronary heart disease.;3 Aimed to investigate whether epicardial adipose tissue volume (EATV) and epicardial adipose tissue (EAT)-derived inflammatory cytokines are correlated with character of plaque and vascular postive remodeling in patients presenting with coronary heart disease (CHD) underwent CABG.Research SubectsParti:301 Patients who were undergoing Digital subtraction angiography(DSA) and dual-source CT were collected from Apirl 2010 to October in 2013. Part2: Adipose tissue from total 80 patients who were undergoing CABG and Valve Replacement were collected from December 2012 to October 2013.Research Methods1. All patients underwent anthropometric measurements and routine laboratory tests, including blood fat and cholesterol, complete blood cell counts, dual-source cardiac CT and 91 patients with newly diagnosed essential hypertension underwent ambulatory blood pressure monitoring for 24 h.2. Epicardial adipose tissue volume (EATV) determined by a 64-slice dual-source Cardiac CT scanner(Somatom Denition, Siemens Medical Solutions, Forchheim, Germany) then using Syngo MMWP(VE32B)workstation Circulation software anzyling character of plaque and measuring index of vascular remodling.3. All CHD patients were confirmed by DSA.4. Another 91 patients with hypertension were divided into four groups according to quartiles of EATV, and differences of 24 ABPM parameters of four groups were observed, These patients were categorized into three groups according to their BP pattern (group 1, dipper hypertension; group 2, non-dipper hypertension; group 3, anti-dipper hypertension;).5. Samples of adipose tissue were collected during CABG and valve replacement operations. These specimens were divided into two portions. One portion was frozen in liquid nitrogen and stored at-80℃ for protein and mRNA extraction. The other portion was fixed in formalin for immunohistochemical analysis.6. ELISA Data Calculation for Inflammatory Cytokines in Plasma which were collected before operation7. Data were statistically analyzed by software of SPSS19.0.Results1.EATV of hypertension group was significantly higher than that of the non-hypertension group [(103.85±41.32) vs (92.35±41.59) cm3, P<0.05]. After adjusting obesity, diabetes and other cardiovascular risk factors, EATV still was an independent risk factor affecting the occurrence of hypertension (P<0.05); EATVs of non-dipper hypertension group and anti-dipper hypertension group were significantly higher than that of dipper hypertension group among patients receiving dynamic electrocardiogram examinationa[(108.26±31.06)、(119.83±28.45)VS(99.26±29.45) cm3, both P<0.05].24-hour average systolic blood pressure (24hSBP),24-hour average diastolic blood pressure (24hDBP), daytime average SBP (dSBP), daytime average DBP (dDBP), nighttime average SBP (nSBP),nighttime average DBP (nDBP) and other parameters of four groups which were divided in accordance with quartiles of EATV progressively increased with the increasing of EATV (all P< 0.01).2. Coronary heart disease was associated with EATV. Incidence proportion of coronary heart disease and EATV both showed a significant increasing trend when age increased (P= 0.001) in the total population. EATV still was an independent risk factor after adjust traditional risk factors (OR=1.006, P=0.045);3. Incidence proportion of coronary heart disease and EATV both showed a significant increasing trend when age increased (P<0.05)4. There were significant gender differences of EATV and incidence of coronary heart disease between the younger group with other age groups in which EATV and Incidence proportion of coronary heart disease was no Statistically significant difference(P> 0.05);The significant differences between male’s EATV with CAD and non-CAD group,but the significant differences were not observed in female group(male:P= 0.026, female:P> 0.05).The EATVs were significantly higher in the CHD group compared to those of the NCHD group.5.Subgroup analysis of the CHD patients demonstrated that EATV in patients with positive remodeling was significantly higher(127.63±42.00cm3 vs.95.49±25.36 cm3)than that of the non-positive remodeling group. Lipid plaque volume was positively correlated with EATV (p=0.002,r=0.34); however,fiber plaque volume was negatively correlated with EATV(p=0.0077,r=-0.30)..Logistic regression analysis indicated that EATV is an independent risk factor for positive vascular remodeling.6.Compared to 40 NCHD-VHD patients, the 40 CHD patients who received CABG surgery, presented higher levels of mRNA and protein expression of leptin and MMP9 in EAT (p<0.01). However, there was no significant difference (p> 0.05) in mRNA and protein expression of leptin and MMP9 withinthe TAT of CABG and VHDpatients. In the CABG group, leptin and MMP9 levels in EAT and EATV were positively correlated with lipid plaque volume and negative correlated with fibrous plaque volume (p<0.05).Conclusion1.The increasing EATV is associated with the occurrence of hypertension, and the increasing EATV can aggravate the abnormal circadian rhythm of blood pressure. EATV was elevated in newly diagnosed and untreated patients with non-dipper hypertension and anti-dipper hypertension. EATV can be used to indicate the increased risk of target organ.;2.EATV was an risk factor of CAD. CAD and EATV presented an significant increasing trend when age increased; Male’s EATV was significantly higher than that of female in below 60 year; EATV and coronary heart disease seemed more closely linked with men, especially in people below 60 year;3. Epicardial adipose tissue volume (EATV) and EAT-derived inflammatory cytokines were significantly correlated with plaque vulnerability in coronary heart disease (CHD).It has been determined that EATV was an independent risk factor for both CHD and plaque vulnerability.4. EATV was positively correlated with lipid plaque volume and negatively with fibrous plaque volume in CABG patients.5. Hypertension, Lipid plaque volume and,plasame MMP9、leptin influenced vascular positive remodeling.Logistic regression analysis indicated that EATV,MMP9,leptin devired from EAT were independent risk factors for vascular positive remodeling. |
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