AIM: Telomeres are DNA-protein structures protecting chromosome ends from degradation and fusion. Telomere Length Shortening (TLS) is not only crucial for cellular senescence but it has been also identified as a marker of multiple chronic diseases, including cardiovascular (CV) disease. Effects on TLS by multiple classical risk factors have been demonstrated, although that of elevated LDL cholesterol (LDL-C) has been not investigated so far.
METHODS: To explore whether elevated LDL-C associates with TLS and whether it can cause TLS in Familial Hypercholesterolemia (FH), TL was measured by PCR on mononuclear cells-derived genomic DNA from 141 heterozygous hypercholesterolemia patients (HeFH) (probands for mutations in LDLR, APOB and PCSK9 loci, determined via genome sequencing) and 79 non HeFH-patients characterized by elevated LDL-C. Clinical, pharmacological history, Dutch Lipid Clinic Score (DLCS) were collected for diagnosis of FH and biochemical parameters were determined for each subject.
RESULTS: TL was not different in HeFH compared to non FH-patients, although older (4716 vs 3718 respectively, p<0.001) and with higher LDL-C (242.2065.56 vs 201.8456.64 mg/dL respectively, p<0.001). Independently from statin treatment, upon matching by age and by LDL-C, a TLS was observed in HeFH vs non-FH (1.290.45 vs 1.540.32, p= 0.010). No other clinical and biochemical parameters correlated with TL and TLS both in hypercholesterolemia and HeFH.
CONCLUSIONS: In light of these data, genetically determined hypercholesterolemia results in TLS, supporting premature cellular ageing in FH.