Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

Balistreri, Carmela Rita; Ruvolo, Giovanni; Lio, Domenico; Madonna, Rosalinda

doi:10.1016/j.yjmcc.2017.06.011

Cited by 51 publications

(85 citation statements)

References 161 publications

(320 reference statements)

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“…To determine the effects of irbesartan on inflammation induced by hypoxia we have chosen to measure mRNA levels of two TLRs, TLR-2 and -4, which activation by an ischemic injury aggravate tissue damage [ 23 , 24 ]. In particular, TLR-4 and its downstream targets such as TNF-α and i-NOS are found to facilitate the inflammatory reaction in clinical ischemic condition, i.e.…”

Section: Resultsmentioning

confidence: 99%

AT1-receptor blockade: Protective effects of irbesartan in cardiomyocytes under hypoxic stress

et al. 2018

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Hypoxia induces myocardial injury through the activation of inflammatory and oxidative processes. The pivotal role of the renin angiotensin system (RAS) in the pathogenesis of cardiovascular diseases has been firmly established in clinical trials and practice; in fact many experimental and clinical data have highlighted that its inhibition has a cardioprotective role. Activated RAS also stimulates inflammation directly inducing proinflammatory and oxidative gene expression. This study aimed to investigate the protective role of a pre-treatment (10 and 100 μM) with irbesartan on injury induced by 24 h of hypoxia in HL-1 cardiomyocytes; in particular, we have analyzed the natriuretic peptide (BNP) expression, a biomarker able to modulate inflammatory reaction to cardiac injury and some markers involved in oxidative stress and inflammation. Our results demonstrated that a pre-treatment with 100 μM irbesartan significantly increased SOD activity and catalase expression of 15 and 25%, respectively, compared to hypoxic cells (P<0.05). On the other hand, it was able to reduce the release of peroxynitrite and iNOS protein expression of 20 and 50% respectively (P<0.05). In addition irbesartan exerts an anti-inflammatory activity reducing Toll-like receptors (TLRs)-2 and -4 mRNA expression, TNF-alpha expression and activity (20%) and increasing the expression of the cytokine IL-17 (40%) (P<0.05 vs hypoxia). Our findings also showed that BNP induced by ischemia was significantly and in a concentration-dependent manner reduced by irbesartan. The findings of our study demonstrated that the AT1 receptor antagonist irbesartan exerts a protective role in an in vitro hypoxic condition reducing oxidative stress and inflammation.

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Section: Resultsmentioning

confidence: 99%

AT1-receptor blockade: Protective effects of irbesartan in cardiomyocytes under hypoxic stress

et al. 2018

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“…Consequently, further and larger investigations are certainly needed. For example, genomic, transcriptomic and epigenetic investigations may eventually lead to a better understanding of the molecular and cellular mechanisms associated with AAA in BAV patients 28 .…”

Section: Discussionmentioning

confidence: 99%

Deregulation of Notch1 pathway and circulating endothelial progenitor cell (EPC) number in patients with bicuspid aortic valve with and without ascending aorta aneurysm

Balistreri

Crapanzano

Schirone

et al. 2018

Sci Rep

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Bicuspid aortic valve (BAV) is frequently associated with the development of ascending aortic aneurysm, even if the underlying mechanisms remain to be clarified. Here, we investigated if a deregulation of Notch1 signaling pathway and endothelial progenitor cells (EPCs) number is associated with BAV disease and an early ascending aortic aneurysm (AAA) onset. For this purpose, 70 subjects with BAV (M/F 50/20; mean age: 58.8 ± 14.8 years) and 70 subjects with tricuspid aortic valve (TAV) (M/F 35/35; mean age: 69.1 ± 12.8 years) and AAA complicated or not, were included. Interestingly, patients with AAA showed a significant increase in circulating Notch1 levels and EPC number than subjects without AAA. However, circulating Notch1 levels and EPC number were significantly lower in BAV subjects than TAV patients either in the presence or absence of AAA. Finally, Notch pathway was activated to a greater extent in aortic aneurysmatic portions with respect to healthy aortic fragments in both BAV and TAV patients. However, the expression of genes encoding components and ligands of Notch pathway in aortic tissues was significantly lower in BAV than TAV subjects. Our study demonstrates that BAV subjects are characterized by a significant decrease in both tissue and circulating levels of Notch pathway, and in blood EPC number than TAV patients, either in presence or absence of AAA disease.

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“…NK cells strongly express TLR1 [ 12 ]. It is well known that some diseases are associated with TLRs activation, such as neuroinflammation, cardiovascular diseases and cancers [ 43 , 44 , 45 ].…”

Section: Toll-like Receptormentioning

confidence: 99%

The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive Phytochemicals Targeting the TLR4 Signaling Pathway

Chen

Kao

Liu

2018

IJMS

266

143

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Toll-like receptors (TLRs) are a well-known family of pattern recognition receptors that play an important role in a host immune system. TLR triggering leads to the induction of pro-inflammatory cytokines and chemokines, driving the activation of both innate and adaptive immunity. Recently, an increasing number studies have shown the link between TLRs and cancer. Among them, the toll-like receptor 4 (TLR4) signaling pathway is associated with inflammatory response and cancer progression. Dietary phytochemicals are potential modulators of immunological status with various pharmacological properties including anti-cancer, anti-oxidant and anti-inflammatory. Curcumin, 6-gingerol, 6-shogaol, 1-dehydro-10-gingerdione, epigallocatechin gallate (EGCG), luteolin, quercetin, resveratrol, caffeic acid phenethyl ester, xanthohumol, genistein, berberine, and sulforaphane can inhibit TLR4 activation. The aim of the present review is to describe the role of the TLR4 signaling pathway between inflammatory response and cancer progression. We further introduce bioactive phytochemicals with potential anti-inflammation and chemoprevention by inhibiting TLR activation.

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Toll-like receptor-4 signaling pathway in aorta aging and diseases: “its double nature”

Cited by 51 publications

References 161 publications

AT1-receptor blockade: Protective effects of irbesartan in cardiomyocytes under hypoxic stress

AT1-receptor blockade: Protective effects of irbesartan in cardiomyocytes under hypoxic stress

Deregulation of Notch1 pathway and circulating endothelial progenitor cell (EPC) number in patients with bicuspid aortic valve with and without ascending aorta aneurysm

The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive Phytochemicals Targeting the TLR4 Signaling Pathway

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