Biomarkers for vascular ageing in aorta tissues and blood samples

• Published in: Experimental gerontology Vol. 128; p. 110741
• Main Authors: Buffa, Silvio, Borzì, Davide, Chiarelli, Rita, Crapanzano, Floriana, Lena, Anna Maria, Nania, Martina, Candi, Eleonora, Triolo, Fabio, Ruvolo, Giovanni, Melino, Gerry, Balistreri, Carmela Rita
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.12.2019
• Subjects: Endothelium age-related impairment; EPC cell populations; Inflammatory cytokines; Notch and TLR4; SA-β-Gal activity; TP53, p21 and p16 genes; EPC cell populations; Inflammatory cytokines; SA-β-Gal activity; Endothelium age-related impairment; Notch and TLR4; TP53, p21 and p16 genes
• ISSN: 0531-5565; 1873-6815; 1873-6815
• DOI: 10.1016/j.exger.2019.110741

Functional and quantitative alterations and senescence of circulating and expanded endothelial progenitor cells (EPC), as well as systemic and tissue modifications of angiogenetic and inflammatory molecules, were evaluated for predicting age-related vessel wall remodeling, correlating them to intima media thickness (IMT) in the common carotid artery (CCA), a biomarker of early cardiovascular disease and aortic root dilation. A homogenous Caucasian population was included in the study, constituted by 160 healthy subjects (80 old subjects, mean age 72 ± 6.4, range 66–83 years; and 80 younger blood donors, mean age 26.2 ± 3.4, range 21–33 years), and 60 old subjects (mean age 73 ± 1.4 (range 66–83) years) with aortic root dilatation and hypertension, and 60 old people (70 ± 2.8 (age range 66–83)) with sporadic ascending aorta aneurysm (AAA). In addition, 20 control individuals (10 men and 10 women, mean age: 65 ± 8), were also included in the study for evaluating the gene expression's levels, in aorta tissues. Appropriate techniques, practises, protocols, gating strategies and statistical analyses were performed in our evaluations. Interestingly, old people had a significantly reduced functionality and a high grade of senescence (high SA-β-Gal activity and high levels of TP53, p21 and p16 genes) of EPC expanded than younger subjects. The values of related parameters progressively augmented from the old subjects, in good healthy shape, to subjects with hypertension and aorta dilation, and AAA. Moreover, they significantly impacted the endothelium than the alterations in EPC number. No changes, but rather increased systemic levels of VEGF and SDF-1 were also assessed in old people vs. younger donors. Old people also showed significantly increased systemic levels of inflammatory cytokines, and a reciprocal significant reduction of systemic s-Notch 1 than younger subjects. These parameters, also including the number EPC alterations, resulted to be significantly sustained in old people bearers of an inflammatory combined genotype. Consistent with these data, a reduced expression of Notch-1 gene, accompanied by a sustained expression of inflammatory genes (i.e. TLR4, IL-1β, IL-6 and IL-17) were detected in aortic tissues from old control people and AAA cases. Finally, we detected the biological effects induced by all the detected alterations on vessel wall age-related remodeling, by evaluating the IMT in the population studied and correlating it to these alterations. The analysis demonstrated that the unique independent risk predictors for vascular ageing are age, the EPC reduced migratory activity and senescence, high grade of expression of genes inducing EPC senescence and chronic tissue and systemic inflammation. Thus, we propose these parameters, of easy determination in biological samples (i.e. blood and tissue samples) from alive human population, as optimal biomarkers for vascular ageing. •Age-related endothelium impairment characterises ageing process•The examination of EPC populations demonstrated reduced circulating levels in old than younger subjects•They are significantly associated with a decreased gene expression and function of Notch 1 pathway•Reciprocally, an increased systemic and gene expression of TLR4 pathway and inflammatory cytokines were observed in old people•Thus, we suggested that the key cross-talk of the conserved evolutionarily Notch1 and TLR4 pathways is crucial in age-related endothelium impairment