## 2 Characteristics of PVAT  
Obesity causes the dispersal of a visceral adipose tissue affected by systemic insulin resistance, dyslipidemia, with increased levels of proinflammatory cytokines and modified secretome. PVAT seems to share its origin with vascular smooth muscle cells and not with visceral or subcutaneous adipose tissue. PVAT consists of adipocytes, stromal cells with pre-adipocytes, fibroblasts, stem cells, inflammatory cells (macrophages, lymphocytes, and eosinophils), nerves, and vascular cells [2]. In rodents, PVAT shows many similarities with brown adipose tissue due to its well-vascularized structure and adipose morphology, whereas in humans PVAT resembles visceral adipose tissue [11]. Extrapolation of rodent studies to humans is frequently deceptive in the research of either adipose tissues or inflammatory responses [12]. Insufficient data on the appearance of PVAT is caused by these disparities between human and animal models. The shortage of human studies on PVAT has been caused by the lack of proper tools, but the advance of imaging techniques has already begun to change that [11]. The inflammation caused by obesity changes the appearance of PVAT. As the macrophages of the adipose tissue turn from anti-inflammatory (M2) into pro-inflammatory (M1), the PVAT of obese individuals shows higher levels of M1 polarized macrophages than in lean individuals. Therefore, PVAT has smaller adipocytes and lower levels of intracellular lipid accumulation. Obesity induces a whitening of brown adipose tissue in some vascular segments, such as thoracic periaortic adipose tissue [2,11]. Aortic coarctation models in rats show a decreased number of adipocyte progenitor cells, with lower adipocyte formation and lipid accumulation. Differences in arterial pressure modify the adipogenic potential and stress relaxation in aortic PVATs [13]. PVAT surrounding different blood vessels has a heterogeneous density and appearance, resembling endothelial cells and smooth muscle cells from different vascular beds. In human coronary arteries, PVAT has diverse-shaped and smaller adipocytes with decreased adipogenic differentiation [14]. In patients with abdominal aortic aneurysm, adipocytes are larger than in healthy individuals [15]. In atherosclerosis, the amount of PVAT correlates directly with the size of atherosclerotic plaque found in the corresponding vascular wall. In coronary artery disease, enlarged PVAT as measured on CT imaging or in post-mortem human coronary artery samples has higher volume near coronary artery segments with an atherosclerotic plaque as compared with no plaque areas. Plaque composition is also relevant for the structural changes of PVAT. Plaque with a lipid core and calcification was shown to be associated with an increased PVAT mass and macrophage infiltration in PVAT [16]. 3 The Anti-Inflammatory Role of Ghrelin in Adipose Tissue Macrophage Infiltration in Atherosclerosis  
PVAT surrounding arteries may be involved in building up atherosclerotic plaque from outside the artery through infiltration of macrophages and proinflammatory factors. However, the reciprocal may be also true, and atherosclerosis may be the cause of inflammation in PVAT, as an expression of the bidirectional crosstalk between PVAT and the vascular wall. Adipocytokines secreted by PVAT may diffuse into the vascular wall and draw macrophages. The PVAT on the atherosclerotic segments of the aorta has more macrophages as compared to atherosclerosis-free arteries in the same patient. In the epicardial adipose tissue of patients with coronary atherosclerosis, the number of pro-inflammatory M1 macrophages is more pronounced than in controls. The inflammation of PVATs is correlated with adventitial inflammation and atherosclerosis [16]. In coronary artery disease (CAD), secretion of adipocytes is higher in PVAT near non-stenoic than near stenotic coronary artery segments in patients undergoing coronary artery bypass graft surgery.