Elevated Wall Tension Leads to Reduced miR-133a in the Thoracic Aorta by Exosome Release
| Autor: | Walker M. Blanding, Jeffrey A. Jones, Jean Marie Ruddy, Michael R. Zile, Rupak Mukherjee, Adam W. Akerman, John S. Ikonomidis, Elizabeth K. Nadeau, Robert E. Stroud |
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| Rok vydání: | 2018 |
| Předmět: |
Male
exosome secretion medicine.medical_specialty Immunoblotting Aorta Thoracic 030204 cardiovascular system & hematology Exosome 03 medical and health sciences Mice 0302 clinical medicine Aneurysm thoracic aorta Internal medicine medicine.artery medicine Thoracic aorta Animals Humans Exome RNA Messenger Cells Cultured 030304 developmental biology Original Research 0303 health sciences Aortic Aneurysm Thoracic microRNA business.industry Vascular biology vascular biology Fibroblasts medicine.disease Vessel diameter Mice Inbred C57BL Disease Models Animal MicroRNAs Gene Expression Regulation Hypertension Cardiology Dilation (morphology) Mir 133a Female wall tension Cardiology and Cardiovascular Medicine business Basic Science Research |
| Zdroj: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| ISSN: | 2047-9980 |
| Popis: | Background Reduced miR‐133a was previously found to be associated with thoracic aortic ( TA ) dilation, as seen in aneurysm disease. Because wall tension increases with vessel diameter (Law of Laplace), this study tested the hypothesis that elevated tension led to the reduction of miR‐133a in the TA . Methods and Results Elevated tension (1.5 g; 150 mm Hg) applied to murine TA ex vivo reduced miR‐133a tissue abundance compared with TA held at normotension (0.7 g; 70 mm Hg). Cellular miR‐133a levels were reduced with biaxial stretch of isolated murine TA fibroblasts, whereas smooth muscle cells were not affected. Mechanisms contributing to the loss of miR‐133a abundance were further investigated in TA fibroblasts. Biaxial stretch did not reduce primary miR‐133a transcription and had no effect on the expression/abundance of 3 micro RNA ‐specific exoribonucleases. Remarkably, biaxial stretch increased exosome secretion, and exosomes isolated from TA fibroblasts contained more miR‐133a. Inhibition of exosome secretion prevented the biaxial stretch‐induced reduction of miR‐133a. Subsequently, 2 in vivo models of hypertension were used to determine the effect of elevated wall tension on miR‐133a abundance in the TA : wild‐type mice with osmotic pump–mediated angiotensin II infusion and angiotensin II –independent spontaneously hypertensive mice. Interestingly, the abundance of miR‐133a was decreased in TA tissue and increased in the plasma in both models of hypertension compared with a normotensive control group. Furthermore, miR‐133a was elevated in the plasma of hypertensive human subjects, compared with normotensive patients. Conclusions Taken together, these results identified exosome secretion as a tension‐sensitive mechanism by which miR‐133a abundance was reduced in TA fibroblasts. |
| Databáze: | OpenAIRE |
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