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Elevated Wall Tension Leads to Reduced miR-133a in the Thoracic Aorta by Exosome Release.

Abstract：

: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.

journal_name

J Am Heart Assoc

journal_title

Journal of the American Heart Association

authors

Akerman AW,Blanding WM,Stroud RE,Nadeau EK,Mukherjee R,Ruddy JM,Zile MR,Ikonomidis JS,Jones JA

doi

10.1161/JAHA.118.010332

subject

Has Abstract

pub_date

2019-01-08 00:00:00

pages

e010332

issue

issn

2047-9980

journal_volume

pub_type

杂志文章

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Elevated Wall Tension Leads to Reduced miR-133a in the Thoracic Aorta by Exosome Release.