Cross-talk between inflammation and angiotensin II: studies based on direct transfection of cardiomyocytes with AT1R and AT2R cDNA.

Abstract

Ischemic myocardium exhibits inflammation, local angiotensin II (Ang II) generation and up-regulation of LOX-1, a lectin-like ox-LDL receptor. To define the inter-active roles of Ang II and inflammation in furthering tissue injury, cultured HL-1 cardiomyocytes were treated with Ang II. Ang II treatment up-regulated the expression of Ang II type 1 (AT1R) and type 2 (AT2R) receptors as well as LOX-1. Ang II also activated p44/42MAPK, p38MAPK, c-Jun and NF-κB, and increased the expression of inflammation-related genes (interleukins-6, interleukins-10, tumor necrosis factor-α, intercellular adhesion molecule-1). To study how inflammation per se might affect expression of Ang II receptors and LOX-1, cultured, cardiomyocytes were treated with lipopolysaccharide (LPS). Like Ang II, LPS increased the expression of AT1R, AT2R and LOX-1. LPS also activated mitogen-acticated protein kinase (MAPKs), c-Jun and NF-κB, and pro-inflammatory genes. The selective inhibitors of MAPKs, c-Jun and NF-κB each blocked the transcription of LOX-1 and pro-inflammatory genes in response to Ang II as well as LPS. These observations suggested a positive feedback between Ang II and inflammation. To delineate the role of AT1R and AT2R in LOX-1 expression, another set of cardiomyocytes were transfected with AT1R or AT2R cDNA. Forced over-expression of AT1R resulted in activation of MAPKs, c-Jun and NF-κB, up-regulation of inflammatory genes and LOX-1; on the other hand forced AT2R over-expression induced up-regulation of pro-apoptotic signals (pro-IL-1β and IL-1β), and decreased LOX-1 expression. These studies show that both Ang II and inflammation mediator LPS up-regulate AT1R, AT2R and LOX-1 expression. Up-regulation of AT1R promotes inflammation and LOX-1 expression, whereas up-regulation of AT2R promotes apoptosis signals and decreases LOX-1 expression.

• Authors: Xianwei Wang, Magomed Khaidakov, Zufeng Ding, Sona Mitra, Jingjun Lu, Shijie Liu, Jawahar L Mehta
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 237 Issue 12 Pg. 1394-401 (Dec 2012) ISSN: 1535-3699 [Electronic] England
• PMID: 23354398 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cytokines
• DNA, Complementary
• Inflammation Mediators
• Lipopolysaccharides
• NF-kappa B
• Olr1 protein, mouse
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Scavenger Receptors, Class E
• Angiotensin II
• Extracellular Signal-Regulated MAP Kinases

Topics

• Angiotensin II (genetics, metabolism)
• Animals
• Apoptosis (drug effects, genetics)
• Cell Line
• Cytokines (biosynthesis, genetics)
• DNA, Complementary (genetics)
• Extracellular Signal-Regulated MAP Kinases (genetics, metabolism)
• Inflammation (genetics, metabolism, pathology)
• Inflammation Mediators (metabolism)
• Lipopolysaccharides (pharmacology)
• Mice
• Myocytes, Cardiac (metabolism, pathology)
• NF-kappa B (genetics, metabolism)
• Receptor, Angiotensin, Type 1 (biosynthesis, genetics)
• Receptor, Angiotensin, Type 2 (biosynthesis, genetics)
• Scavenger Receptors, Class E (biosynthesis, genetics)
• Signal Transduction (drug effects, genetics)
• Up-Regulation