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

Ruvolo G, Pisano C, Candore G, Lio D, Palmeri C, Maresi E, Balistreri CR - Mediators Inflamm. (2014)

Bottom Line: 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.It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

View Article: PubMed Central - PubMed

Affiliation: Unit of Cardiac Surgery, Department of Surgery and Oncology, University of Palermo, 90127 Palermo, Italy.

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.

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Related in: MedlinePlus

Morphometric quantification of lymphocytes, T cell subpopulations, and macrophages in aorta samples of cases with high responder genotype, other genotypes, and controls. CD3, CD4, CD8, CD20, and CD68 positive cells in media and adventitia and in 10 contiguous high-power fields (magnification 400x) were counted by two independent observers. Significant increased amounts of CD3+CD4+CD8+CD68+CD20+ cells were observed by comparing their values among the three groups (by ANOVA test). In particular, cases with high responder genotype had higher numbers of these cells than controls and cases with other genotypes.
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fig3: Morphometric quantification of lymphocytes, T cell subpopulations, and macrophages in aorta samples of cases with high responder genotype, other genotypes, and controls. CD3, CD4, CD8, CD20, and CD68 positive cells in media and adventitia and in 10 contiguous high-power fields (magnification 400x) were counted by two independent observers. Significant increased amounts of CD3+CD4+CD8+CD68+CD20+ cells were observed by comparing their values among the three groups (by ANOVA test). In particular, cases with high responder genotype had higher numbers of these cells than controls and cases with other genotypes.

Mentions: In order to validate the biological effect mediated of combined risk genotype on the levels of systemic plasma inflammatory mediators, we also compared inflammatory/immune infiltrate between patients bearing high responder genotype and those with other genotypes. According to encouraging data obtained on levels of systemic plasma inflammatory mediators, we assessed a higher inflammatory/immune infiltrate in tissue aorta samples from patients bearing high responder genotype than those bearing other genotypes and control aortas (see Figure 3). Positive correlation was identified between the number of CD3+CD4+CD8+ CD68+ cells observed in aorta samples from patients bearing high responder genotype and the histological abnormalities observed through histopathological and immunohistochemical assays and Tunel testing (see Table 6). As reported in Table 6, the number of CD3+CD4+CD8+ CD68+ cells also correlated with the increased plasma levels of IL-6, TNF-α, CRP, and MMP-2 and -9.


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

Ruvolo G, Pisano C, Candore G, Lio D, Palmeri C, Maresi E, Balistreri CR - Mediators Inflamm. (2014)

Morphometric quantification of lymphocytes, T cell subpopulations, and macrophages in aorta samples of cases with high responder genotype, other genotypes, and controls. CD3, CD4, CD8, CD20, and CD68 positive cells in media and adventitia and in 10 contiguous high-power fields (magnification 400x) were counted by two independent observers. Significant increased amounts of CD3+CD4+CD8+CD68+CD20+ cells were observed by comparing their values among the three groups (by ANOVA test). In particular, cases with high responder genotype had higher numbers of these cells than controls and cases with other genotypes.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4120489&req=5

fig3: Morphometric quantification of lymphocytes, T cell subpopulations, and macrophages in aorta samples of cases with high responder genotype, other genotypes, and controls. CD3, CD4, CD8, CD20, and CD68 positive cells in media and adventitia and in 10 contiguous high-power fields (magnification 400x) were counted by two independent observers. Significant increased amounts of CD3+CD4+CD8+CD68+CD20+ cells were observed by comparing their values among the three groups (by ANOVA test). In particular, cases with high responder genotype had higher numbers of these cells than controls and cases with other genotypes.
Mentions: In order to validate the biological effect mediated of combined risk genotype on the levels of systemic plasma inflammatory mediators, we also compared inflammatory/immune infiltrate between patients bearing high responder genotype and those with other genotypes. According to encouraging data obtained on levels of systemic plasma inflammatory mediators, we assessed a higher inflammatory/immune infiltrate in tissue aorta samples from patients bearing high responder genotype than those bearing other genotypes and control aortas (see Figure 3). Positive correlation was identified between the number of CD3+CD4+CD8+ CD68+ cells observed in aorta samples from patients bearing high responder genotype and the histological abnormalities observed through histopathological and immunohistochemical assays and Tunel testing (see Table 6). As reported in Table 6, the number of CD3+CD4+CD8+ CD68+ cells also correlated with the increased plasma levels of IL-6, TNF-α, CRP, and MMP-2 and -9.

Bottom Line: 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.It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

View Article: PubMed Central - PubMed

Affiliation: Unit of Cardiac Surgery, Department of Surgery and Oncology, University of Palermo, 90127 Palermo, Italy.

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.

Show MeSH
Related in: MedlinePlus