LPS and oxLDL-induced S100A12 and RAGE expression in carotid arteries of atherosclerotic Yucatan microswine.

Abstract

BACKGROUND:

S100A12, also known as Calgranulin C, is a ligand for the receptor for advanced glycation end products (RAGE) and plays key roles in cardiovascular and other inflammatory diseases. Interactions between S100A12 and RAGE initiate downstream signaling activating extracellular signal-regulated kinases (ERK1/2), mitogen activated protein kinases (MAPK), and transcription factor NF-κB. This increases the expression of pro-inflammatory cytokines to induce the inflammatory response. S100A12, and RAGE play a critical role in the development and progression of atherosclerosis. There is a well-known relationship between the bacterial endotoxin lipopolysaccharide (LPS) and the lipid antigens oxidized low-density lipoprotein (oxLDL) in driving the immune response in atherosclerosis.

METHODS AND RESULTS:

Our study aimed to compare the potential of LPS and oxLDL in regulating the expression of S100A12 and RAGE in atherosclerosis. The expression of these proteins was assessed in the harvested carotid arteries from LPS- and oxLDL-treated atherosclerotic Yucatan microswine. Tissues were collected from five different treatment groups: (i) angioplasty alone, (ii) LPS alone, (iii) oxLDL alone, (iv) angioplasty with LPS, and (v) angioplasty with oxLDL. Immunohistochemical findings revealed that angioplasty with LPS induced higher expression of S100A12 and RAGE compared to other treatment groups. The results were further corroborated by testing their gene expression through qPCR in cultured vascular smooth muscle cells (VSMCs) isolated from control carotid arteries and LPS- and oxLDL-treated arteries.

CONCLUSIONS:

The results of this study suggest that LPS induces the expression of S100A12 and RAGE more than oxLDL in atherosclerotic artery and both S100A12 and RAGE could be therapeutic targets.

• Authors: Harbinder Singh, Vikrant Rai, Devendra K Agrawal
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 49 Issue 9 Pg. 8663-8672 (Sep 2022) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 35771356 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• Lipopolysaccharides
• Lipoproteins, LDL
• Receptor for Advanced Glycation End Products
• S100A12 Protein
• oxidized low density lipoprotein
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Atherosclerosis (genetics, metabolism)
• Carotid Arteries
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Lipopolysaccharides (pharmacology)
• Lipoproteins, LDL (metabolism, pharmacology)
• Receptor for Advanced Glycation End Products (genetics, metabolism)
• S100A12 Protein (genetics, metabolism)
• Swine
• Swine, Miniature