Effects of oxidative stress, exercise and cardiac rehabilitation on telomerase in T-lymphocytes

Abstract

Myocardial infarction (MI) remains the primary cause of death worldwide, despite significant medical advances. Lymphocytes play a key role in both the pathogenesis of atherosclerosis and also the healing process following MI. It has been found however, that decreased lymphocyte telomere length correlates with greater risk of MI and worse outcomes. Atherosclerosis is causally linked with MI and can be triggered by myeloid and lymphoid cells, which destabilise and rupture lipid-rich plaques on the arterial wall. Atherosclerosis is also linked with elevated oxidative stress, increasing the risk of cardiovascular disease. Experiments in-vitro have shown that even mild oxidative stress caused telomere shortening and inhibits cell proliferation. Oxidative stress in-vivo can be caused by physical inactivity, which can contribute to atherosclerosis. Telomere length can be maintained by regular physical activity. My results show that hyperoxia enhanced IFN-γ mRNA transcription in Tlymphocytes, whereas hypoxia significantly reduced inflammation. Oxidative stress suppressed a) in-vitro T-cell proliferation in a TERT-dependent way, b) telomerase activity and c) TERT expression in mTert-GFP+ mice by 5-fold (P<0.01) compared to hypoxia. MAPK inhibition (MAPKi) down-regulated IFN-γ mRNA transcription and enhanced splenocyte proliferation equally under both hypoxia and hyperoxia. MAPKi enhanced telomerase activity under hyperoxia by day 10 in culture and significantly increased telomerase activity by day 14 compared to hypoxia. The effect of MAPKi seems to require the presence of TERT and interaction between cells. Voluntary wheel running led to increased telomerase activity in ApoE-/-mTert-GFP+ mice on a high fat diet (HFD) compared to the no exercise group. HFD enhanced both telomerase activity and B-cell numbers under exercise compared to the same mice on a normal diet (ND). In humans, regulatory T-cells were elevated in the acute stage of MI and decreased by 7-fold (P<0.001) following cardiac rehabilitation. However, no significant effect was observed on telomerase activity.