Local and systemic effects of visceral and perivascular adipose tissue

Rather than being solely a storage depot for triglycerides, adipose tissue is able to secrete pro- and anti-inflammatory cytokines and adipokines. A state of low grade inflammation associated with excess adipose tissue is involved in the increase in the incidences of atherosclerotic diseases and type 2 diabetes that accompany obesity. The adipose tissue surrounding the arteries, perivascular adipose tissue, is suggested to influence the vascular wall by inducing a local pro-inflammatory environment. Cross sections of the left anterior descending artery perivascular were investigated in post mortem cases with atherosclerosis. The amount of perivascular adipose tissue is related to the size and composition of atherosclerotic plaques. Also inflammation of perivascular adipose tissue, determined by macrophage infiltration is associated with the amount and composition of atherosclerotic plaques. In subjects with coronary atherosclerosis, pro-inflammatory CD11c+ macrophages are sparse in pvAT compared to anti-inflammatory CD206+ macrophages. CD206+ macrophages in pvAT and the adventitia are related to plaque inflammation and the presence of a lipid core. In patients undergoing coronary artery bypass grafting, perivascular adipose tissue biopsies were harvested near stenotic and non-stenotic coronary artery segments. Surprisingly, multiple adipocytokines such as interleukin 1α and interleukin 5 were secreted at higher levels by perivascular adipose tissue near non-stenotic than near stenotic coronary artery segments. This may reflect a down-regulation of the pro-inflammatory response in advanced atherosclerosis as anti-inflammatory macrophages are more abundant in perivascular adipose tissue of these patients. However, a difference in the number of M2 macrophages in perivascular adipose tissue near stenotic and non-stenotic coronary artery segments could not be demonstrated. In addition, absence of perivascular adipose tissue at coronary artery segments covered by a myocardial bridge is associated with a lack of atherosclerosis. This was determined on computed tomography-scans by measuring the calcium score and determining the presence of atherosclerotic plaques in bridged coronary artery segments. Altogether, these results indicate potential involvement of pvAT in coronary atherosclerotic plaque development, although the causality of the relation has yet to be determined. In obese subjects the peripheral tissues become insulin resistant. Insulin resistance is accompanied by a cluster of metabolic changes, often referred to as the metabolic syndrome. The metabolic syndrome is associated with an increased cardiovascular risk in patients with manifest arterial disease. In patients with manifest arterial disease without known diabetes, insulin resistance increases with the number of metabolic syndrome components, and elevated insulin resistance increases the risk of new cardiovascular events. The relation between insulin resistance and cardiovascular events is independent of the components of the metabolic syndrome. Furthermore, patients with manifest arterial disease with the highest plasma high sensitivity C-reactive protein (hsCRP) levels, indicating low grade inflammation, were at the highest risk to develop type 2 diabetes. In addition they were more insulin resistant as compared to those with low hsCRP levels. This increase in risk is more pronounced in females than in males and is not modified by statin use. In conclusion, adipose tissue is able to induce effects leading to atherosclerosis and diabetes on a local and systemic level.