Lack of Rab27a attenuates foam cell formation and macrophage inflammation in uremic apolipoprotein E knockout mice.

Abstract

As the most common cardiovascular disease, atherosclerosis (AS), is a leading cause of high mortality in patients with chronic renal failure. Rab27a has been reported to regulate the progression of cardiovascular and renal diseases. Nevertheless, little studies investigated the role and mechanism of Rab27a in uremic-accelerated AS (UAAS). An animal model of UAAS was established in apolipoprotein E knockout (apoE-/-) mice using 5/6 nephrectomy (NX). We conducted in vitro and in vivo functional experiments to explore the role of Rab27a in UAAS, including the presence of oxidized low-density lipoprotein (ox-LDL). Rab27a expression was upregulated in the plaque tissues of NX apoE-/- mice. The knockout of Rab27a (Rab27a-/-) reduced AS-induced artery injury, as manifested by the reductions of plaque area, collagen deposition, inflammation and lipid droplet. Besides, cholesterol efflux was increased, while the expression of lipid metabolism-related proteins and the secretions of pro-inflammatory factors were decreased in ox-LDL-induced NX Rab27a-/- apoE-/- mice group. Further, Rab27a deletion inhibited the activation of nuclear factor κB (NF-κB) pathway. In conclusion, our study indicated that Rab27a deficiency attenuated foam cell formation and macrophage inflammation, depending on the NF-κB pathway activation, to inhibit AS progression in uremic apoE-/- mice. This finding may provide a new targeting strategy for UAAS therapy.

• Authors: Yan Shen, Yajuan Gao, Jiani Fu, Cui Wang, Yali Tang, Shengnan Chen, Yan Zhao
• Journal: Journal of molecular histology (J Mol Histol) Vol. 54 Issue 3 Pg. 183-193 (Jun 2023) ISSN: 1567-2387 [Electronic] Netherlands
• PMID: 37166546 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• NF-kappa B
• Apolipoproteins E
• Apolipoproteins
• Rab27a protein, mouse
• rab27 GTP-Binding Proteins

Topics

• Animals
• Mice
• Mice, Knockout
• Foam Cells (metabolism)
• NF-kappa B (metabolism)
• Atherosclerosis (genetics, metabolism)
• Macrophages (metabolism)
• Inflammation (metabolism)
• Apolipoproteins E (genetics, metabolism)
• Apolipoproteins (metabolism)
• rab27 GTP-Binding Proteins (metabolism)