Telomeric non-coding RNA and senescence gene dysregulation in acute coronary syndrome: insights into novel biomarkers and therapeutic targets

Background The telomere complex, crucial for cellular senescence and genomic stability, has become a promising target for anti-aging therapies in chronic age-associated diseases. Recently, telomeric non-coding RNA (TERRA) has been implicated in the regulation of telomere homeostasis and replicative senescence. However, its role, along with senescence-related genes, in atherosclerotic cardiovascular disease remains unexplored. Purpose This study explored the interplay between leukocyte telomere length (LTL), collective TERRA levels transcribed from multiple chromosome ends (1q, 2q, 4q, 10q, 13q and 22q), and markers of senescence (p21Cip1 and p16lnk4A) in patients with acute coronary syndrome (ACS) or stable angina (SA). Methods Consecutive patients undergoing coronary angiography were enrolled and divided into three groups: 98 patients (81 male; 62 ± 9 years) with ACS (ST-elevation myocardial infarction, non-ST-segment elevation myocardial infarction, unstable angina), 87 patients (71 male; 65 ± 9 years) with SA, and 39 patients (22 male; 63 ± 10 years) with normal coronary arteries (NCA). LTL measurement, TERRA, p16INK4a and p21Cip1 expression were assessed in whole blood obtained before coronary angiography using quantitative real-time PCR assays. Results Patients with ACS had significantly lower LTL (p=0.02) and higher TERRA (p=0.0001), compared to those with NC. Additionally, ACS patients exhibited increased expression of p16INK4a (p=0.0002) and low expression of p21Cip1 (p=0.0001) as compared to NCA. A strong correlation was observed between TERRA levels and p16lnk4A (r=0.638, p=0.0001). Multivariable logistic regression analysis showed higher median TERRA significantly associated with increased risk of ACS (OR = 4.5, 95%CI = 1.8-11.7, p = 0.0016). Conclusions Our findings reveal abnormal expression of TERRA and cellular senescence markers in patients with ACS. These results highlight potential therapeutic strategies targeting the telomere complex and senescence-related signaling to prevent the onset and progression of atherosclerotic disease.