Adventitial fibroblasts in vascular structure and function: the role of oxidative stress and beyond

The vascular adventitia, defined as the area between the external elastic lamina and the outermost edge of the blood vessel, is composed primarily of fibroblasts and for years was thought to be merely a passive structural support for the blood vessel. Consequently, studies pertaining to the role of the adventitia in regulating vascular function have been far outnumbered by those regarding the vascular endothelium. However, recent work has begun to reveal the dynamic properties of the adventitia. It was therefore the aim of this review to provide an overview of the existing knowledge demonstrating the role of the adventitia in regulating vessel structure and function. The main topics covered in this review include the cellular composition of the adventitia and the role of the adventitia in vascular oxidative stress, vasomotor responses, extracellular matrix protein expression, growth factor expression, and endothelin-1 (ET-1) expression. Recent evidence suggests that the adventitia is a major producer of vascular reactive oxygen species. It displays a distinct response to injury, hypoxia, and pulmonary hypertension, mediating vascular remodelling, repair, and extracellular matrix deposition. It may also play a role in regulating vascular tone. More recently, it has been reported that adventitial fibroblasts can produce ET-1 after Ang II treatment. Additionally, emerging evidence suggests that the adventitia may be a potent source of vasoactive hormones such as growth factors and ET-1, which may regulate vascular structure and function via autocrine or paracrine signalling mechanisms. Despite these findings, many important questions regarding the role of the vascular adventitia remain unanswered, suggesting the need for further research to determine its exact function in health and disease.