Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, Johannesburg, 2193, South Africa.
Eur J Appl Physiol. 2013 Nov;113(11):2803-11. doi: 10.1007/s00421-013-2722-8. Epub 2013 Sep 6.
The mechanisms responsible for telomere shortening in heart failure are uncertain. We evaluated whether left ventricular (LV) dilatation and systolic chamber dysfunction produced by chronic β-adrenergic receptor (β-AR) activation is associated with leukocyte or cardiac telomere shortening.
Following 6 months of daily injections of the β-AR agonist, isoproterenol (0.02 mg/kg/day) or the saline vehicle to rats, the extent of LV dilatation and LV systolic chamber dysfunction were determined using echocardiography and isolated perfused heart procedures, and relative telomere length of leukocyte (LTL) and cardiac (CTL) deoxyribonucleic acid were determined using a quantitative real-time polymerase chain reaction assay.
β-AR activation resulted in LV dilatation as indexed by increased LV diastolic diameters (9.2 ± 0.6 vs. 8.4 ± 0.9 mm, P = 0.01) and increased diastolic volume intercepts at zero pressure of the LV diastolic pressure-volume relationship (isolated, perfused heart preparation) (0.40 ± 0.06 vs. 0.37 ± 0.08 ml, P = 0.03). Moreover, β-AR activation resulted in LV systolic chamber dysfunction as indexed by reductions in LV endocardial fractional shortening (0.40 ± 0.05 vs. 0.45 ± 0.06, P = 0.01) and the slope of the LV systolic pressure-volume relation (609 ± 176 vs. 901 ± 230, P = 0.01). Although LTL decreased with age in rats receiving either the β-AR agonist or the saline vehicle (P < 0.05), neither CTL (-0.10 ± 0.14 vs. -0.15 ± 0.12, P = 0.3) nor LTL (-0.11 ± 0.19 vs. -0.15 ± 0.18, P = 0.5) were modified by β-AR activation.
In conclusion, chronic β-AR activation sufficient to produce LV dilatation and systolic chamber dysfunction is not associated with alterations in leukocyte or cardiac telomere length. Telomere shortening in chronic heart failure is unlikely to be attributed to chronic β-AR activation.
心力衰竭导致端粒缩短的机制尚不确定。我们评估了慢性β-肾上腺素能受体（β-AR）激活引起的左心室（LV）扩张和收缩室功能障碍是否与白细胞或心脏端粒缩短有关。
在大鼠接受每日β-AR 激动剂异丙肾上腺素（0.02mg/kg/天）或生理盐水载体 6 个月后，通过超声心动图和分离灌注心脏程序确定 LV 扩张和 LV 收缩室功能障碍的程度，并使用定量实时聚合酶链反应测定白细胞（LTL）和心脏（CTL）脱氧核糖核酸的相对端粒长度。
β-AR 激活导致 LV 扩张，表现为 LV 舒张直径增加（9.2 ± 0.6 与 8.4 ± 0.9mm，P = 0.01）和 LV 舒张压力-容积关系的舒张容积截距增加（分离、灌注心脏制备）（0.40 ± 0.06 与 0.37 ± 0.08ml，P = 0.03）。此外，β-AR 激活导致 LV 收缩室功能障碍，表现为 LV 心内膜分数缩短减少（0.40 ± 0.05 与 0.45 ± 0.06，P = 0.01）和 LV 收缩压力-容积关系斜率降低（609 ± 176 与 901 ± 230，P = 0.01）。尽管在接受β-AR 激动剂或生理盐水载体的大鼠中，LTL 随年龄增长而降低（P < 0.05），但 CTL（-0.10 ± 0.14 与-0.15 ± 0.12，P = 0.3）和 LTL（-0.11 ± 0.19 与-0.15 ± 0.18，P = 0.5）均不受β-AR 激活的影响。
总之，足以导致 LV 扩张和收缩室功能障碍的慢性β-AR 激活与白细胞或心脏端粒长度的改变无关。慢性心力衰竭中的端粒缩短不太可能归因于慢性β-AR 激活。
