Histologic identification of brown adipose and peripheral nerve involvement in human atherosclerotic vessels

Abstract

The disease mechanisms and histology of plaque development associated with atherosclerosis remain incredibly complex and not entirely understood. Recent investigations have emphasized the importance of inflammation in atherosclerosis. Several studies have also indicated heterotopic, or extraskeletal, bone formation in atherosclerotic vessels. The mechanisms behind heterotopic ossification (HO) appear to have similarities to those underlying atherosclerosis, with inflammation being a key inductive component to HO. Therefore, in the present study, we evaluated the histology associated with pathologies of atherosclerosis and HO in 271 coronary vessel tissue samples. We examined the prevalence and features of the inflammatory response, as well as new vessel and bone formation. Inflammation and neovascularization was observed both in the adventitia and within the atherosclerotic lesions of the vessels themselves. Intriguingly, neural changes, including collections of inflammatory cells and expression of neuro-inflammatory factors, were detected in the adventitial nerves of the vessels. Mature lamellar bone was found in 18 coronary vessels (7%), often with hematopoietic elements and active bone remodeling. Brown adipocytes, which pattern heterotopic bone formation, were present within the atherosclerotic lesions (28%, 75/271). As expected, there was a strong correlation between the presence of cholesterol and plaque formation (P<0.0001), but there also seemed to be a trend towards a connection between the presence of brown adipocytes and plaque. From this histological evaluation, along with cholesterol and dystrophic calcification, we noted a novel appearance of brown adipocytes, as well as neural changes, which may provide new insights to further our understanding of atherosclerosis.

Partial Agonist, Telmisartan, Maintains PPARγ Serine 112 Phosphorylation, and Does Not Affect Osteoblast Differentiation and Bone Mass

“…Thus, these two proteins represent factors which combine both, improvement in energy metabolism and positive regulation of bone mass. It has been reported that extraskeletal bone formation in either atherosclerotic vessels or in heterotopic bone is associated with a presence of adipocytes with brown phenotype suggesting their positive effect on tissue calcification [55] , [56] . Although in the presented studies we did not observe bone anabolic activity of TEL, we cannot exclude that prolonged therapeutic use of TEL may be beneficial for bone by inducing bone anabolic activity in fat cells including marrow adipocytes.…”

Perivascular fat, AMP‐activated protein kinase and vascular diseases

“…Such a disparity may be due to the method of harvesting the adipose tissue or to inter‐individual variations in fat tissue distribution (Miao and Li, ). Interestingly, a very recent study has identified a strong correlation between presence of brown adipocytes and atherosclerotic plaque in 271 samples of human coronary artery (Salisbury et al ., ). The authors speculate that as brown adipocytes are involved in neovascularization, they may have an important role to play in vascular remodelling in diseases such as atherosclerosis.…”

Anatomical Locations of Human Brown Adipose Tissue

“…Human epicardial fat in type 2 diabetic and metabolic syndrome patients with coronary atherosclerosis (CAD) expressed amounts of UCP1 similar to those expressed in control subjects without diabetes, metabolic syndrome, and CAD (20). Brown adipocytes have been observed in histology sections of human CAD plaques at autopsy (43). The role and significance of PVAT and perivascular BAT per se in vascular biology and pathophysiology remain to be clarified.…”