TERT assists GDF11 to rejuvenate senescent VEGFR2+/CD133+ cells in elderly patients with myocardial infarction

Hypofunction of Circulating Endothelial Progenitor Cells and Aggravated Severity in Elderly Male Patients With Non-ST Segment Elevation Myocardial Infarction: Its Association With Systemic Inflammation

“…Circulating EPCs are critical for repairing endothelial damage and associated with prognosis of coronary artery diseases (21). Previous studies revealed that aging had close relationship with circulating EPC dysfunction (22,23), and late-outgrowth EPC function significantly decreased in aging AMI (8). In the present study, we found that circulating EPC activity was significantly reduced in aging NSTEMI patients compared to young group and there was negative correlation between circulating EPC function and age.…”

“…Our previous investigation illuminated that aging led to mitigating EPC function via the CXCR4 pathway (7). It is reported that the function of late EPCs is subdued in elderly patients with acute myocardial infarction (AMI) (8), but other investigators found that the number of circulating CD34+CD133+ progenitor cells is not related to age after AMI (9). Because there is a great distinction in pathogenesis between ST-segment elevation myocardial infarction (STEMI) and NSTEMI, the effect of aging on EPC function in NSTEMI patients and its underlying mechanism are still unclear.…”

Canonical and extra‐telomeric functions of telomerase: Implications for healthy ageing conferred by endurance training

“…Conversely, vascular function and angiogenesis were impaired in TERT-depleted endothelial progenitor cells in vitro (Zhao et al, 2019), F I G U R E 2 Summary of the key non-canonical functions of telomerase relevant to endurance training adaptations. (a) TERT binds to Sp1 and transcribes its target genes DNMT3B (Yu et al, 2018) and VEGF (Liu et al, 2016) thereby contributing to de novo DNA methylation changes and angiogenesis, respectively.…”

“…The angiogenesis relied on TERT, but not its catalytic activity, as an hTERT mutant (lacking telomere synthesis capabilities) stimulated angiogenesis, which indicated a telomere length‐independent effect (Liu et al, 2016 ). In a clinical study, TERT up‐regulation facilitated growth differentiation factor 11 (GDF11)‐mediated restoration of VEGFR2 + /CD133 + cells isolated from older adult patients who had suffered myocardial infarctions via eNOS and SMAD 2/3 signalling (Zhao et al, 2019 ). Conversely, vascular function and angiogenesis were impaired in TERT‐depleted endothelial progenitor cells in vitro (Zhao et al, 2019 ), consistent with other findings (Liu et al, 2016 ).…”

“…In a clinical study, TERT up‐regulation facilitated growth differentiation factor 11 (GDF11)‐mediated restoration of VEGFR2 + /CD133 + cells isolated from older adult patients who had suffered myocardial infarctions via eNOS and SMAD 2/3 signalling (Zhao et al, 2019 ). Conversely, vascular function and angiogenesis were impaired in TERT‐depleted endothelial progenitor cells in vitro (Zhao et al, 2019 ), consistent with other findings (Liu et al, 2016 ). Using a mouse model of hindlimb ischemia (surgical removal of femoral artery), adenovirus vector treatment with human VEGF 165 enhanced skeletal muscle TERT protein expression, telomerase activity, capillarisation and survival in Wistar rats (Zaccagnini et al, 2005 ).…”