Glucocorticoids Regulate the Vascular Remodeling of Aortic Dissection Via the p38 MAPK-HSP27 Pathway Mediated by Soluble TNF-RII

Abstract

Increasing researches suggest that inflammatory response is involved in vascular remodeling, which plays an important role in the development of aortic dissection. Glucocorticoids have been widely used in the clinical practice due to its powerful and effective anti-inflammatory property. However, the potential relationship between glucocorticoids and aortic dissection was still obscure. This study sought to elucidate the effect of glucocorticoids on the development and progression of aortic dissection, and the potential mechanism involved. Serum cortisol in aortic dissection patients was significantly higher than that in non-ruptured aortic aneurysm patients and healthy volunteers by radioimmunoassay. In modified C57BL/6 mouse model of aortic dissection, glucocorticoids reduced the incidence of aortic dissection and protected the collagen from degradation. Furthermore, glucocorticoids inhibited the TNF-α secretion of THP-1 monocytes, decreased the migration, phenotype switch from contractile type to synthetic type, and the apoptosis of human aortic smooth muscle cells induced by TNF-α. Finally, TNF-sRII was identified as an important cytokine in cellular interaction that participated in vascular remodeling by targeting the p38 MAPK-HSP27 pathway. These results indicate that glucocorticoids inhibit the incidence of aortic dissection by decreasing the TNF-α secretion and increasing the uncombined TNF-sRII, positively participating in vascular remodeling.

Regulatory Master Genes Identification and Drug Repositioning by Integrative mRNA-miRNA Network Analysis for Acute Type A Aortic Dissection

“…As mentioned above, calcium channel blocker TL_HRAS26 which regulates calcium signals might act as a potential drug for ATAAD. A recent study showed that glucocorticoids regulate the vascular remodeling of aortic dissection, (Zhang et al, 2018) our results also indicated that hydrocortisone hemisuccinate might be a useful drug by activating glucocorticoid receptor. Previous research demonstrated that aorta samples are mainly made up of aortic smooth muscle cells, fibroblasts and endothelial cells.…”

Hydrogen Sulfide Attenuates Aortic Remodeling in Aortic Dissection Associating with Moderated Inflammation and Oxidative Stress through a NO-Dependent Pathway

“…The external aortic diameter of the mice was measured in three transverse sections using image J software (National Institutes of Health), as described previously [ 21 ].The ascending aorta was defined as the proximal 2-mm section from the ostium of the innominate artery, the aortic arch as the section between the ostia of the left common carotid artery and left subclavian artery, and the descending aorta as the distal 2-mm section from the ostium of the left subclavian artery.…”

The Role of Macrophages in Aortic Dissection

“…Increased glucocorticoids reduce the marginalization, extravasation and local activation of macrophages, thereby inhibiting MMP-2 secretion and thus protecting collagen degradation. These findings indicate that glucocorticoids and TNF-sRII may be interesting targets for future AD intervention (Zhang et al, 2018).…”