Adventitial Fibroblasts in Aortic Aneurysm: Unraveling Pathogenic Contributions to Vascular Disease

Aortic aneurysm (AA) is a degenerative vascular disease that involves aortic dilatation, and, if untreated, it can lead to rupture. Despite its significant impact on the healthcare system, its multifactorial nature and elusive pathophysiology contribute to limited therapeutic interventions that prevent the progression of AA. Thus, further research into the mechanisms underlying AA is paramount. Adventitial fibroblasts are one of the key constituents of the aortic wall, and they play an essential role in maintaining vessel structure and function. However, adventitial fibroblasts remain understudied when compared with endothelial cells and smooth muscle cells. Adventitial fibroblasts facilitate the production of extracellular matrix (ECM), providing structural integrity. However, during biomechanical stress and/or injury, adventitial fibroblasts can be activated into myofibroblasts, which move to the site of injury and secrete collagen and cytokines, thereby enhancing the inflammatory response. The overactivation or persistence of myofibroblasts has been shown to initiate pathological vascular remodeling. Therefore, understanding the underlying mechanisms involved in the activation of fibroblasts and in regulating myofibroblast activation may provide a potential therapeutic target to prevent or delay the progression of AA. This review discusses mechanistic insights into myofibroblast activation and associated vascular remodeling, thus illustrating the contribution of fibroblasts to the pathogenesis of AA.