Are the leukocyte telomere length attrition and telomerase activity alteration potential predictor biomarkers for sporadic TAA in aged individuals?

Abstract

A large variability in occurrence, complications, and age/gender manifestations characterizes individual susceptibility of sporadic thoracic aortic aneurysms (TAA), even in subjects with the same risk factor profiles. The reasons are poorly understood. On the other hand, TAA pathophysiology mechanisms remain unclear than those involved in abdominal aorta aneurysms. However, recent evidence is suggesting a crucial role of biological ageing in inter-individual risk variation of cardiovascular diseases, including sporadic TAA. Biological age rather than chronological age is a better predictor of vascular risk. Relevant assumptions support this concept. In confirming this evidence and our preliminary data, the mean of blood leukocyte telomere length, through use of terminal restriction fragment assay and in blood samples from sporadic TAA patients and controls, was examined. Telomerase activity was also analyzed in two groups. In addition, we verified the weight of genetic inflammatory variants and the major TAA risk factors in telomere/telomerase impairment. Aorta histopathological abnormalities and systemic inflammatory mediators were ultimately correlated with telomere/telomerase impairment. Data obtained demonstrated shorter telomeres and a reduced telomerase activity in TAA patients significantly associated with a genetic inflammatory risk profile, age, gender, smoking, hypertension, a histopathological phenotype, and higher levels of systemic inflammatory mediators than controls. In conclusion, telomere and telomerase activity's detection might be used as predictor biomarkers of sporadic TAA. Their impairment also suggests a strong role of vascular ageing in sporadic TAA, evocated by both environmental and genetic inflammatory factors.

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

“…Interestingly, we found that their combined genotype was significantly represented in sporadic TAA than controls. In subsequent investigations, we also have shown that cases with this risk genotype showed a higher systemic inflammatory mediator levels [8,126], a significant inflammatory/immune infiltrate [8,126],a typical MD phenotype [127], a lower telomere length [128,129] and positive correlations with histopatological abnormalities [126,127],hypertension, smoking, and aging [8,[126][127][128][129]. Consequently, our findings (even if prevalently of associated type) led us to suggest the key role of TLR-4 pathway in the onset of this disease [4,8].…”

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

“…Furthermore, we detected that these alleles influence vascular biological aging, evaluating the gold standard aging marker, the telomere length, in a small number of cases and controls, selected randomly, but having the same age and gender. It characterized the 85% of the cases examined, which had lower telomere length, higher levels of mediators, increased amount of chronic inflammatory infiltrate [33,66,67].…”

Anti-Inflamm-Ageing and/or Anti-Age-Related Disease Emerging Treatments: A Historical Alchemy or Revolutionary Effective Procedures?

“…Accordingly, it has been demonstrated that in peripheral blood mononuclear cells from aged individuals, the exercise training reduces protein expression of TLR-2 and TLR-4 [ 78 ]. Similarly, physical exercise also seems to improve the circulating levels of endothelial progenitor cells (EPCs), cells related to both endothelial turnover, cardiovascular repair and regeneration, and adult angiogenesis [ 18 ]. Thus, physical exercise is associated with a good health of endothelium, an essential component of stroma of all tissues and organs [ 18 ].…”

“…Similarly, physical exercise also seems to improve the circulating levels of endothelial progenitor cells (EPCs), cells related to both endothelial turnover, cardiovascular repair and regeneration, and adult angiogenesis [ 18 ]. Thus, physical exercise is associated with a good health of endothelium, an essential component of stroma of all tissues and organs [ 18 ]. Its dysfunction has been detected to contribute to the onset of the major number of ARDs, CVDs, and neurodegenerative diseases included, as amply described in our recent studies [ 13 , 18 ].…”