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

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 appear to have similarities to those underlying atherosclerosis, with inflammation being a key inductive component to heterotopic ossification. Therefore, in the present study, we evaluated the histology associated with pathologies of atherosclerosis and heterotopic ossification 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 were 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 neuroinflammatory 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%, or 75/271). As expected, there was a strong correlation between the presence of cholesterol and plaque formation (P < .0001), but there also seemed to be a trend toward a connection between the presence of brown adipocytes and plaque. From this histologic 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.