Convergence of endothelial dysfunction, inflammation and glucocorticoid resistance in depression-related cardiovascular diseases

Major Depressive Disorder, or depression, has been extensively linked to dysregulated HPA axis function, chronic inflammation and cardiovascular diseases. While the former two have been studied in depth, the mechanistic connection between depression and cardiovascular disease is unclear. As major mediators of vascular homeostasis, vascular pathology and immune activity, endothelial cells represent an important player connecting the diseases. Exaggerated inflammation and glucocorticoid function are important topics to explore in the endothelial response to MDD. Glucocorticoid resistance in several cell types strongly promotes inflammatory signaling and results in worsened severity in many diseases. However, endothelial health and inflammation in chronic stress and depression are rarely considered from the perspective of glucocorticoid signaling and resistance. In this review, we aim to discuss (1) endothelial dysfunction in depression, (2) inflammation in depression, (3) general glucocorticoid resistance in depression and (4) endothelial glucocorticoid resistance in depression co-morbid inflammatory diseases. We will first describe vascular pathology, inflammation and glucocorticoid resistance separately in depression and then describe their potential interactions with one another in depression-relevant diseases. Lastly, we will hypothesize potential mechanisms by which glucocorticoid resistance in endothelial cells may contribute to vascular disease states in depressed people. Overall, endothelial-glucocorticoid signaling may play an important role in connecting depression and vascular pathology and warrants further study.