Shear stress imposed by blood flow is crucial for maintaining vascular homeostasis. We examined the role of shear stress in regulating SIRT1, an NAD + -dependent deacetylase, and its functional relevance in vitro and in vivo. The application of laminar flow increased SIRT1 level and activity, mitochondrial biogenesis, and expression of SIRT1-regulated genes in cultured endothelial cells (ECs). When the effects of different flow patterns were compared in vitro, SIRT1 level was significantly higher in ECs exposed to physiologically relevant pulsatile flow than pathophysiologically relevant oscillatory flow. These results are in concert with the finding that SIRT1 level was higher in the mouse thoracic aorta exposed to atheroprotective flow than in the aortic arch under atheroprone flow. Because laminar shear stress activates AMP-activated protein kinase (AMPK), with subsequent phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser-633 and Ser-1177, we studied the interplay of AMPK and SIRT1 on eNOS. Laminar flow increased SIRT1-eNOS association and eNOS deacetylation. By using the AMPK inhibitor and eNOS Ser-633 and -1177 mutants, we demonstrated that AMPK phosphorylation of eNOS is needed to prime SIRT1-induced deacetylation of eNOS to enhance NO production. To verify this finding in vivo, we compared the acetylation status of eNOS in thoracic aortas from AMPKα2 −/− mice and their AMPKα2 +/+ littermates. Our finding that AMPKα2 −/− mice had a higher eNOS acetylation indicates that AMPK phosphorylation of eNOS is required for the SIRT1 deacetylation of eNOS. These results suggest that atheroprotective flow, via AMPK and SIRT1, increases NO bioavailability in endothelium.NAD + -dependent deacetylase | AMP-activated protein kinase | endothelial nitric oxide synthase | NO bioavailability | endothelial homeostasis S IRT1, also known as Sirtuin 1 (silent mating type information regulation 2 homolog), contributes to the caloric restriction (CR)-induced increase in lifespan in species ranging from yeast to mammals (1-3). Functioning as an NAD + -dependent class III histone deacetylase (4), SIRT1 deacetylates multiple targets in mammalian cells, including tumor suppressor p53, Forkhead box O1 and 3 (FOXO1 and FOXO3), peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α), liver X receptor, and hypoxia-inducible factor 2α (5-14). By regulating these molecules involved in cell survival and in carbohydrate and lipid metabolism, SIRT1 functions as a master regulator of stress response and energy homeostasis.SIRT1 is also an important modulator in cardiovascular functions in health and disease. The beneficial effects of SIRT1 on endothelial cell (EC) biology were demonstrated by several previous studies. Ota et al. (15) showed that overexpression of SIRT1 prevented oxidative stress-induced endothelial senescence, whereas inhibition of SIRT1 led to premature senescence. Treatment of human coronary arterial ECs with resveratrol (RSV), an SIRT1 activator, increased the mitochondrial mass and ke...

These preliminary data suggest that the use of MSCs could provide potential benefits in renal transplantation by reducing the dosage of conventional immunosuppressive drug that is required to maintain long-term graft survival and function.

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Chronic obstructive pulmonary disease (COPD) is characterized by a chronic inflammatory response that is worsened by acute exacerbations. Lianhuaqingwen (LHQW) has anti-inflammatory and immune regulatory functions and may inhibit the airway inflammation that occurs during an acute exacerbation of COPD. In this study, 100 participants were recruited and randomly assigned, 1 : 1, to the LHQW and the conventional groups, which were treated, respectively, with LHQW capsules and conventional Western medicine or only conventional Western medicine. The scores of the CAT scale and levels of inflammatory cytokines in blood and sputum were measured during treatment. In addition, subjects were subdivided into high-risk and low-risk subgroups. The CAT scores in the LHQW group and high-risk subgroup were clearly improved from the 5th day, but the other groups improved only after treatment was completed. Expression levels of IL-8, TNF-α, IL-17, and IL-23 in the sputum and of IL-8 and IL-17 in the blood were significantly decreased after treatment, and similar results were found in subgroups. These data suggested that LHQW capsules can accelerate the improvement of AECOPD patients, especially for the high-risk subgroup, and the mechanism of action may be related to the decreased release of inflammatory mediators.