Lipopolysaccharides, but not Angiotensin ll, lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Abstract

Angiotensin II (Ang II) might induce pro-inflammatory effects directly in the vascular wall independently of its haemodynamic effects. The aim of our study was to investigate the putative direct pro-inflammatory and vasomotor effects of Ang II and compare to those of lipopolysaccharides (LPS) in mouse isolated mesenteric resistance-sized arteries (MRA) supported by experiments in cultured human primary endothelial and vascular smooth muscle cells. Results showed that 24-hr organ culture of mouse MRA with 10 nM Ang II had, unlike 100 ng/mL LPS, no effects on IL-6 or MCP-1 secretion, VCAM1 mRNA expression or endothelial function, while Ang II significantly decreased maximal vasomotor responses to phenylephrine. In support, 24-hr organ culture of mouse MRA significantly suppressed Agtr1a mRNA and augmented Tlr4 mRNA along with attenuated vasomotor responses to Ang II. Moreover, contrary to LPS and TNF-α, Ang II and [Sar1]-Ang II had no concentration- or time-dependent effects on IL-6 and MCP-1 secretion in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMC). AGTR1 or AGTR2 mRNA expression was undetectable in HUVEC, whereas HASMC expressed only AGTR1 mRNA. In summary, contrary to previous studies and the observed effects of LPS, we could not demonstrate direct vascular pro-inflammatory effects of Ang II ex vivo or in vitro. As indicated by our results, down-regulation or desensitization of AT R during culture may explain our findings.

Repeated Porphyromonas gingivalis W83 exposure leads to release pro-inflammatory cytokynes and angiotensin II in coronary artery endothelial cells

“…In contrast to the high concentration of Ang II at repeated dose of live bacteria, we found a down regulation of AGTR1 and AGTR2 at the mRNA level. Similar results with human saphenous vein cells (VSMC) and rat aortic smooth muscle (HASMC) suggest that high concentrations of Ang II can induce in vitro gen downregulation or desensitization/internationalization of AGTR1 48,58,59 or AGTR2 57 . However, additional studies are required to identify the role of these receptors in endothelial dysfunction at repeated dose of periodontopathogens.…”

“…Regarding the association between Ang II and the release of proinflammatory molecules such as IL8, IL6 and MCP1, there is no evidence with periodontopathogens, while some evidence have been reported Escheriria coli- LPS ( E. coli-LPS ) 48,58,59 , suggesting a synergistic effect between live- P. gingivalis stimulus and Ang II.…”

“…It has been described that P. gingivalis -LPS is an inducer of tolerance in macrophages, mainly by the suppression of the endothelial recognition receptor (TLR-4) 47,48 ; however, our results showed that LPS (7.0 µg/mL) induced an increase in the release of IL-8 at repeated exposures, which may be related to the type of endothelial recognition receptor to which P. gingivalis -LPS W83 binds (TLR-2) or other factors that may be involved by positively regulating the release of IL-8 49,50 . However, new studies are required to elucidate the mechanism of action.…”

Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway

“…A growing body of evidence suggests that TLR4 modulates endothelial inflammation and atherosclerotic disease [32]. LPS stimulates IL-6, MCP-1 and VCAM-1 mRNA expression in endothelial cells [33]. Isobavachalcone significantly retards leukocyte adhesion to brain endothelial cell via the inhibition of TLR4 signaling [34].…”

The Association of Circulating MiR-29b and Interleukin-6 with Subclinical Atherosclerosis

“…Interestingly, Bacchiega et al found that the IL-6-blocking agent tocilizumab significantly reduced CRP concentrations, together with parameters of systemic inflammation [26]. IL-6 has many other functions, including activation of macrophages [27, 28] and stimulation of endothelial [29, 30] and vascular smooth muscle cells [31, 32]. Although IL-6 and miR-29b both have a number of clear effects on different stages in the formation of atherosclerosis and are, individually, important markers for CVD, we have shown that that the combination of miR-29b and IL-6 offers a better predictive marker for atherosclerosis than either miR-29b or IL-6 alone.…”