ABSTRACT
Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) disrupts peripheral microvascular function. Thrombospondin-1 (TSP-1) is highly expressed during lung injury and has been shown to alter microvascular reactivity. It is unclear exactly how TSP-1 exerts effects on vascular function, but we hypothesized that the TSP-1 receptor CD47 may mediate changes in vasodilation. Wildtype (WT) or CD47 knockout (CD47 KO) C57B6/J-background animals were exposed to 50 µg of MWCNT or saline control via pharyngeal aspiration. Twenty-four hours postexposure, intravital microscopy was performed to assess arteriolar dilation and venular leukocyte adhesion and rolling. To assess tissue redox status, electron paramagnetic resonance and NOx measurements were performed, while inflammatory biomarkers were measured via multiplex assay.Vasodilation was impaired in the WT + MWCNT group compared with control (57 ± 9 vs 90 ± 2% relaxation), while CD47 KO animals showed no impairment (108 ± 8% relaxation). Venular leukocyte adhesion and rolling increased by >2-fold, while the CD47 KO group showed no change. Application of the antioxidant apocynin rescued normal leukocyte activity in the WT + MWCNT group. Lung and plasma NOx were reduced in the WT + MWCNT group by 47% and 32%, respectively, while the CD47 KO groups were unchanged from control. Some inflammatory cytokines were increased in the CD47 + MWCNT group only. In conclusion, TSP-1 is an important ligand mediating MWCNT-induced microvascular dysfunction, and CD47 is a component of this dysregulation. CD47 activation likely disrupts nitric oxide (â¢NO) signaling and promotes leukocyte-endothelial interactions. Impaired â¢NO production, signaling, and bioavailability is linked to a variety of cardiovascular diseases in which TSP-1/CD47 may play an important role.
Subject(s)
CD47 Antigen/metabolism , Endothelium, Vascular/drug effects , Microvessels/drug effects , Nanotubes, Carbon/toxicity , Vasodilation/drug effects , Animals , CD47 Antigen/genetics , Cell Adhesion/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Female , Inhalation Exposure , Leukocyte Rolling/drug effects , Male , Mice, Inbred C57BL , Mice, Knockout , Microvessels/metabolism , Microvessels/physiopathology , Venules/drug effects , Venules/metabolism , Venules/physiopathologyABSTRACT
BACKGROUND: The cardiovascular (CV) and metabolic health benefits or risks associated with consumption of multi-ingredient performance supplements (MIPS) in conjunction with periodized resistance training (RT) in resistance-trained men are unknown. This population is a major target audience for performance supplements, and therefore, the purpose of this study was to investigate the combined effect of RT and commercially available pre- and post-exercise performance supplements on CV health and body fat in resistance-trained men. METHODS: Twenty-four resistance-trained men completed six weeks (three times/week) of periodized RT while either ingesting SHOT 15-min pre-exercise and SYN immediately post-exercise (multi-ingredient performance supplement group: MIPS) or an isocaloric maltodextrin placebo 15-min pre-exercise and immediately post-exercise (Placebo group). Before and after six weeks of RT and supplementation, resting heart rate (HR), blood pressure (BP), total body fat, android fat, gynoid fat, fat-free mass (FFM) and fasting blood measures of glucose, lipids, nitrate/nitrite (NOx), cortisol and high sensitivity C-reactive protein (hs-CRP) were measured. Statistical analysis was conducted using a one-way ANOVA for baseline differences and a 2 × 2 (group × time) repeated measures ANOVA and Tukey post-hoc tests where appropriate. Significance was set at p < 0.05. RESULTS: There was no group × time interaction for HR, BP, blood glucose, lipids, NOx, hs-CRP, cortisol concentrations or body fat. However, there was a time effect where significant decreases in body fat (mean ± SD; MIPS: -1.2 ± 1.2%; Placebo: -0.9 ± 1.1%), android fat (MIPS: -1.8 ± 2.1%; Placebo: -1.6 ± 2.0%), and gynoid fat (MIPS: -1.3 ± 1.6%; Placebo: -1.0 ± 1.4%) for both groups were observed. FFM increased in both groups, and a group × time interaction was observed with MIPS increasing significantly more than the Placebo group (4.2% vs. 1.9%). CONCLUSIONS: Six weeks of MIPS ingestion and periodized RT does not alter CV health parameters or blood indices of health or body fat more than a Placebo treatment in healthy, resistance-trained men. However, MIPS significantly increased FFM more than Placebo.
