Telomerase expression on aortic wall endothelial cells is attenuated in abdominal aortic aneurysms compared to healthy nonaneurysmal aortas

ObjectiveLinear chromosomes carry specific DNA structures at their ends called telomeres. The latter shorten with each successive cell division making their length a marker of cell age. Telomerase prevents such telomere attrition by adding back telomeric repeats at the telomere ends, thus playing an important role in cell aging. On the other hand, an abdominal aortic aneurysm (AAA) represents an age-related degenerative disorder. The aim of the present study was to investigate a potential correlation of telomerase expression with AAA formation.MethodsAortic wall tissue samples were collected from 49 patients (mean age, 63.8 ± 4.4 years) with AAAs during open elective repair and from 24 deceased organ donors as controls (mean age, 60.5 ± 3.9 years). Telomerase expression on endothelial cells was detected by immunohistochemistry. Associations of telomerase positivity with AAAs and epidemiologic and clinical variables were investigated.ResultsTelomerase expression was significantly decreased in patients with AAAs (11 of 49; 22.4%) compared to controls (19 of 24; 79.2%; P < .001). This association persisted after adjustment for age, gender, coronary artery disease (CAD), hypercholesterolemia, hypertension and smoking (odds ratio, 0.47; 95% confidence interval, 0.14-0.58; P < .01.).ConclusionPatients with AAAs have attenuated telomerase endothelial expression compared to controls, implying a protective role of telomerase against AAA formation. Further investigation of pathways involved in vascular aging may contribute to elucidation of AAA pathogenetic mechanisms.

Clinical RelevanceTelomeres are special chromatin structures located at the ends of eukaryotic chromosomes, which shorten with each cell division, thus reflecting cell age. Cells compensate for such a telomere loss by producing telomerase, a reverse transcriptase that adds back telomeric repeats at the telomere ends. Telomerase is considered a key enzyme modulating cell aging, and several studies have associated telomerase function with cardiovascular diseases such as hypertension, atherosclerosis, and stroke. In the present study, telomerase endothelial expression was found to be significantly attenuated in patients with AAAs compared to controls exerting a protective effect against AAA formation. These results are of potential clinical value because they justify further investigation of telomerase expression and possible association with AAAs in more accessible sites (ie, peripheral blood cells) for defining predisposition for AAAs and other diagnostic purposes. In addition, our preliminary data could be potentially useful in the development of telomerase-based treatment modalities for AAAs in the future. For example, maintenance of a youthful phenotype for endothelial cells through preserved telomerase expression might provide a rationale for novel therapeutic strategies in the AAA territory.