Abstract
Vascular remodeling is a pathological condition with structural changes of blood vessels. Both inside-out and outside-in hypothesis have been put forward to describe mechanisms of vascular remodeling. An integrated model of these two hypotheses emphasizes the importance of immune cells such as monocytes/macrophages, T cells, and dendritic cells. These immune cells are at the center stage to orchestrate cellular proliferation, migration, and interactions of themselves and other vascular cells including endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and fibroblasts. These changes on vascular wall lead to inflammation and oxidative stress that are largely responsible for vascular remodeling. Mineralocorticoid receptor (MR) is a classic nuclear receptor. MR agonist promotes inflammation and oxidative stress and therefore exacerbates vascular remodeling. Conversely, MR antagonists have the opposite effects. MR has direct roles on vascular cells through non-genomic or genomic actions to modulate inflammation and oxidative stress. Recent studies using genetic mouse models have revealed that MR in myeloid cells, VSMCs and ECs all contribute to vascular remodeling. In conclusion, data in the past years have demonstrated that MR is a critical control point in modulating vascular remodeling. Studies will continue to provide evidence with more detailed mechanisms to support this notion.
Highlights
At least two different models have been put forward to describe the process of vascular remodeling, the inside-out hypothesis and outside-in hypothesis [5,6]
Monocytes further differentiate into macrophages in the vascular wall and traditionally this process had been considered as a continuous one for the presence of monocytes/macrophages to function without excessive proliferation in the progression of vascular remodeling [8]
Macrophages in this model are mostly regarded as resident ones or being differentiated from monocytes recruited from the vasa vasorum of the adventitia locally
Summary
Mineralocorticoid receptor (MR) is a classic steroid receptor in the nuclear receptor superfamily [15]. To exert its genomic actions, MR binds to mineralocorticoids (primarily aldosterone), translocates into nucleus, binds as homodimers to response elements of target genes, and regulates their expression. The target genes of MR include those important in water-electrolyte homeostasis and blood pressure regulation, inflammation, oxidative stress, and fibrosis [16]. MR has the potential to bind to aldosterone only in tissues that express 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), an enzyme that inactivates glucocorticoids. More recent studies have revealed that vascular cells including VSMCs and ECs express 11βHSD2 as well, indicating that blood vessels are aldosterone-responsive. It remains to be determined whether this enzyme is expressed in macrophages or other immune cells
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