The Biological Parallels Between Atherosclerosis and Cardiac Allograft Vasculopathy: Implications for Solid Organ Chronic Rejection

Atherosclerosis and solid organ chronic rejection are pervasive chronic disease states that account for significant morbidity and mortality in developed countries. Recently, a series of shared molecular pathways have emerged, revealing biological parallels from early stages of development up to the advanced forms of pathology. These shared mechanistic processes are inflammatory in nature, reflecting the importance of inflammation in both disorders. Vascular inflammation triggers endothelial dysfunction and disease initiation through aberrant vasomotor control and shared patterns of endothelial activation. Endothelial dysfunction leads to the recruitment of immune cells and the perpetuation of the inflammatory response. This drives lesion formation through the release of key cytokines such as IFN-y, TNF-alpha, and IL-2. Continued interplay between the adaptive and innate immune response (represented by T lymphocytes and macrophages, respectively) promotes lesion instability and thrombotic complications; hallmarks of advanced disease in both atherosclerosis and solid organ chronic rejection. The aim of this study is to identify areas of overlap between atherosclerosis and chronic rejection. We then discuss new approaches to improve current understanding of the pathophysiology of both disorders, and eventually design novel therapeutics.