Zietzer A, Buschmann E E, Janke D, Li L, Brix M, Meyborg H, Stawowy P, Jungk C, Buschmann I, Hillmeister P
Experimental and Clinical Research Center (ECRC), Richard-Thoma-Laboratories for Arteriogenesis, Center for Cardiovascular Research, Charité - Universitätsmedizin Berlin, Campus Mitte (CCM), Berlin, Germany.
Department for Angiology, Center for Internal Medicine I, Medical University of Brandenburg (MHB), Brandenburg an der Havel, Brandenburg, Germany.
Acta Physiol (Oxf). 2017 Jun;220(2):251-262. doi: 10.1111/apha.12820. Epub 2016 Nov 22.
Physical activity is a potent way to impede vascular ageing. However, patients who suffer from peripheral artery disease (PAD) are often unable to exercise adequately. For those patients, we have developed individual shear rate therapy (ISRT), which is an adaptation of external counterpulsation and enhances endovascular fluid shear stress to increase collateral growth (arteriogenesis). To evaluate the effects of physical exercise and ISRT on the telomere biology of peripheral blood mononuclear cells (PBMCs), we conducted two clinical trials.
In the ISRT-1 study, we assessed PBMC telomerase activity in 26 young healthy volunteers upon a single (short-term) ISRT session and a single treadmill running session. In the ISRT-2 study, we investigated PBMC telomere biology of 14 elderly patients with PAD, who underwent 30 h of (long-term) ISRT within a 5-week period.
We demonstrate that telomerase activity significantly increased from 39.84 Total Product Generated (TPG) Units ± 6.15 to 58.10 TPG ± 10.46 upon a single treadmill running session in healthy volunteers. In the ISRT-2 trial, PBMC telomerase activity and the mRNA expression of the telomere-protective factor TRF2 increased from 40.87 TPG ± 4.45 to 60.98 TPG ± 6.83 and 2.10-fold ± 0.40, respectively, upon long-term ISRT in elderly patients with PAD.
In summary, we show that acute exercise and long-term ISRT positively affect PBMC telomerase activity, which is indicative for an improved regenerative potential of immune cells and vascular tissues. Long-term ISRT also enhances the gene expression of the telomere-protective factor TRF2.
体育活动是延缓血管衰老的有效方法。然而，外周动脉疾病（PAD）患者往往无法进行充分的锻炼。对于这些患者，我们开发了个体化剪切率疗法（ISRT），这是一种外部反搏的改良方法，可增强血管内流体剪切应力以促进侧支生长（动脉生成）。为了评估体育锻炼和ISRT对外周血单个核细胞（PBMC）端粒生物学的影响，我们进行了两项临床试验。
在ISRT-1研究中，我们评估了26名年轻健康志愿者在单次（短期）ISRT治疗和单次跑步机跑步治疗后的PBMC端粒酶活性。在ISRT-2研究中，我们调查了14名老年PAD患者的PBMC端粒生物学，这些患者在5周内接受了30小时的（长期）ISRT治疗。
我们证明，健康志愿者在单次跑步机跑步治疗后，端粒酶活性从39.84总产物生成（TPG）单位±6.15显著增加至58.10 TPG±10.46。在ISRT-2试验中，老年PAD患者在长期ISRT治疗后，PBMC端粒酶活性和端粒保护因子TRF2的mRNA表达分别从40.87 TPG±4.45增加至60.98 TPG±6.83和2.10倍±0.40。
总之，我们表明急性运动和长期ISRT对PBMC端粒酶活性有积极影响，这表明免疫细胞和血管组织的再生潜力得到改善。长期ISRT还增强了端粒保护因子TRF2的基因表达。
