Cells in Atherosclerosis: Focus on Cellular Senescence from Basic Science to Clinical Practice.

Aging is a major risk factor of atherosclerosis through different complex pathways including replicative cellular senescence and age-related clonal hematopoiesis. In addition to aging, extracellular stress factors, such as mechanical and oxidative stress, can induce cellular senescence, defined as premature cellular senescence. Senescent cells can accumulate within atherosclerotic plaques over time and contribute to plaque instability. This review summarizes the role of cellular senescence in the complex pathophysiology of atherosclerosis and highlights the most important senotherapeutics tested in cardiovascular studies targeting senescence. Continued bench-to-bedside research in cellular senescence might allow the future implementation of new effective anti-atherosclerotic preventive and treatment strategies in clinical practice.

Blood flow restriction in human skeletal muscle during rest periods after high-load resistance training down-regulates miR-206 and induces Pax7.

BACKGROUD: Blood flow restriction (BFR) with low-intensity resistance training has been shown to result in hypertrophy of skeletal muscle. In this study, we tested the hypothesis that BFR during the rest periods between acute, high-intensity resistance exercise sessions (70% of 1 repetition maximum, 7 sets with 10 repetitions) enhances the effects of the resistance training. METHODS: A total of 7 healthy young men performed squats, and between sets BFR was carried out on one leg while the other leg served as a control. Because BFR was applied during rest periods, even severe occlusion pressure (approximately 230 mmHg), which almost completely blocked blood flow, was well-tolerated by the participants. Five muscle-specific microRNAs were measured from the biopsy samples, which were taken 2 h after the acute training. RESULTS: Doppler data showed that the pattern of blood flow recovery changed significantly between the first and last BFR. microRNA-206 levels significantly decreased in the BFR leg compared to the control. The mRNA levels of RAC-ß serine/threonine-protein kinase v22, nuclear respiratory factor 1, vascular endothelial growth factor, lupus Ku autoantigen protein p70 genes (p < 0.05), and paired box 7 (p < 0.01) increased in the BFR leg. The protein levels of paired box 7, nuclear respiratory factor 1, and peroxisome proliferator-activated receptor γ coactivator 1α did not differ between the BFR leg and the control leg. CONCLUSION: BFR, during the rest periods of high-load resistance training, could lead to mRNA elevation of those proteins that regulate angiogenesis, mitochondrial biogenesis, and muscle hypertrophy and repair. However, BFR also can cause DNA damage, judging from the increase in mRNA levels of lupus Ku autoantigen protein p70.