title: 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.
authors.affiliation: Unit of Cardiac Surgery, Department of Surgery and Oncology, University of Palermo, 90127 Palermo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ruvolo
authors.affiliation: Unit of Cardiac Surgery, Department of Surgery and Oncology, University of Palermo, 90127 Palermo, Italy.
authors.forename: Calogera
authors.initials: C
authors.lastname: Pisano
authors.affiliation: Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Corso Tukory 211, 90134 Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Candore
authors.affiliation: Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Corso Tukory 211, 90134 Palermo, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Lio
authors.affiliation: Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Corso Tukory 211, 90134 Palermo, Italy.
authors.forename: Cesira
authors.initials: C
authors.lastname: Palmeri
authors.affiliation: Department of Pathologic Anatomy, University of Palermo, 90127 Palermo, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Maresi
authors.affiliation: Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Corso Tukory 211, 90134 Palermo, Italy.
authors.forename: Carmela R
authors.initials: CR
authors.lastname: Balistreri
mesh_terms: D000368:Aged; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology*; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051197:Toll-Like Receptor 4; D020778:Matrix Metalloproteinase 2