| Autor: |
Park SK; Department of Nutrition and Integrative Physiology, University of Utah , Salt Lake City, Utah., La Salle DT; Department of Nutrition and Integrative Physiology, University of Utah , Salt Lake City, Utah.; Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, and Department of Internal Medicine, University of Utah , Salt Lake City, Utah., Cerbie J; Department of Nutrition and Integrative Physiology, University of Utah , Salt Lake City, Utah.; Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, and Department of Internal Medicine, University of Utah , Salt Lake City, Utah., Cho JM; Department of Nutrition and Integrative Physiology, University of Utah , Salt Lake City, Utah., Bledsoe A; Department of Anesthesiology, University of Utah , Salt Lake City, Utah., Nelson A; Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, and Department of Internal Medicine, University of Utah , Salt Lake City, Utah., Morgan DE; Department of Anesthesiology, University of Utah , Salt Lake City, Utah., Richardson RS; Department of Nutrition and Integrative Physiology, University of Utah , Salt Lake City, Utah.; Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, and Department of Internal Medicine, University of Utah , Salt Lake City, Utah.; Division of Geriatrics, Department of Internal Medicine, University of Utah , Salt Lake City, Utah., Shiu YT; Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah , Salt Lake City, Utah., Boudina S; Department of Nutrition and Integrative Physiology, University of Utah , Salt Lake City, Utah.; Division of Endocrinology, Metabolism, and Diabetes, and Molecular Medicine Program, University of Utah School of Medicine , Salt Lake City, Utah., Trinity JD; Department of Nutrition and Integrative Physiology, University of Utah , Salt Lake City, Utah.; Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, and Department of Internal Medicine, University of Utah , Salt Lake City, Utah.; Division of Geriatrics, Department of Internal Medicine, University of Utah , Salt Lake City, Utah., Symons JD; Department of Nutrition and Integrative Physiology, University of Utah , Salt Lake City, Utah.; Division of Endocrinology, Metabolism, and Diabetes, and Molecular Medicine Program, University of Utah School of Medicine , Salt Lake City, Utah. |
| Abstrakt: |
Continuous laminar shear stress increases the process of autophagy, activates endothelial nitric oxide (NO) synthase phosphorylation at serine 1177 (p-eNOS S1177 ), and generates NO in bovine and human arterial endothelial cells (ECs) compared with static controls. However, the translational relevance of these findings has not been explored. In the current study, primary ECs were collected from the radial artery of 7 men using sterile J-wires before (Pre) and after (Post) 60 min of rhythmic handgrip exercise (HG) performed with the same arm. After ECs were identified by positive costaining for vascular endothelial cadherin and 4',6'-diamidino-2-phenylindole, immunofluorescent antibodies were used to assess indices of autophagy, NO generation, and superoxide anion (O 2 ·- ) production. Commercially available primary human arterial ECs were stained and processed in parallel to serve as controls. All end points were evaluated using 75 ECs from each subject. Relative to Pre-HG, HG elevated arterial shear rate ( P < 0.05) ~3-fold, whereas heart rate, arterial pressure, and cardiac output were not altered. Compared with values obtained from ECs Pre-HG, Post-HG ECs displayed increased ( P < 0.05) expression of p-eNOS S1177 , NO generation, O 2 ·- production, BECLIN1, microtubule-associated proteins 1A/1B light chain 3B, autophagy-related gene 3, and lysosomal-associated membrane protein 2A and decreased ( P < 0.05) expression (i.e., enhanced degradation) of the adaptor protein p62/sequestosome-1. These novel findings provide evidence that elevated arterial shear rate associated with functional hyperemia initiates autophagy, activates p-eNOS S1177 , and increases NO and O 2 ·- generation in primary human ECs. NEW & NOTEWORTHY Previously, our group reported in bovine arterial and human arterial endothelial cells (ECs) that shear stress initiates trafficking of the autophagosome to the lysosome and increases endothelial nitric oxide (NO) synthase phosphorylation at serine 1177, NO generation, and O 2 ·- production. Here, the translational relevance of these findings is documented. Specifically, functional hyperemia induced by rhythmic handgrip exercise elevates arterial shear rate to an extent that increases indices of autophagy, NO generation, and O 2 ·- production in primary arterial ECs collected from healthy men. |
