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Can the TLR-4-mediated signaling pathway be "a key inflammatory promoter for sporadic TAA"?

ABSTRACT: Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR-) 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR = 14.4, P = 0.0008) and it represents, together with rs1799752 ACE, rs3918242 MMP-9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

SUBMITTER: Ruvolo G

PROVIDER: S-EPMC4120489 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Can the TLR-4-mediated signaling pathway be "a key inflammatory promoter for sporadic TAA"?

Ruvolo Giovanni G Pisano Calogera C Candore Giuseppina G Lio Domenico D Palmeri Cesira C Maresi Emiliano E Balistreri Carmela R CR

Mediators of inflammation 20140710

Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of ...[more]

PMID: 25120286

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Project description:Inflammatory response plays a bidirectional regulatory role in myocardial infarction (MI). TLR signaling pathway plays an important role in the development of inflammation. Additionally, we discovered that CCRR is an anti-arrhythmic lncRNA in a prior work. Here we show, it is decreased in mice with 3-day MI followed by a sharp increase of pro-inflammatory cytokines and activation of the TLR pathway. Overexpression of CCRR could effectively inhibit the inflammatory response, reduce the infarct area, and improve cardiac function. And also reduced hypoxia-induced inflammation in cardiomyocytes and macrophages induced by IFN and LPS. It produced a similar protective effect in cardiomyocytes co-cultured with macrophages. Through microarray analysis, RNA-binding protein immunoprecipitation analysis, and other related experiments verification, TLR2 and TLR4 may be as potential targets of CCRR after MI. Our findings provide the evidence that lncRNA CCRR plays a key cardioprotective role against MI injury by targeting the TLR signaling pathway. nflammatory response plays a bidirectional regulatory role in myocardial infarction (MI). TLR signaling pathway plays an important role in the development of inflammation. Additionally, we discovered that CCRR is an anti-arrhythmic lncRNA in a prior work. Here we show, it is decreased in mice with 3-day MI followed by a sharp increase of pro-inflammatory cytokines and activation of the TLR pathway. Overexpression of CCRR could effectively inhibit the inflammatory response, reduce the infarct area, and improve cardiac function. And also reduced hypoxia-induced inflammation in cardiomyocytes and macrophages induced by IFN and LPS. It produced a similar protective effect in cardiomyocytes co-cultured with macrophages. Through microarray analysis, RNA-binding protein immunoprecipitation analysis, and other related experiments verification, TLR2 and TLR4 may be as potential targets of CCRR after MI. Our findings provide the evidence that lncRNA CCRR plays a key cardioprotective role against MI injury by targeting the TLR signaling pathway.

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Can the TLR-4-mediated signaling pathway be "a key inflammatory promoter for sporadic TAA"?

Publications

Can the TLR-4-mediated signaling pathway be "a key inflammatory promoter for sporadic TAA"?

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