2026-04-29T00:59:53Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/71382024-10-31T11:55:36Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Caravia, Xurde M
author
Fanjul, Victor
author
Oliver, Eduardo
author
Roiz-Valle, David
author
Morán-Álvarez, Alba
author
Desdín-Micó, Gabriela
author
Mittelbrunn, María
author
Cabo, Roberto
author
Vega, José A
author
Rodríguez, Francisco
author
Fueyo, Antonio
author
Gomez, Monica
author
Lobo-Gonzalez, Manuel
author
Bueno, Hector
author
Velasco, Gloria
author
Freije, José M P
author
Andres, Vicente
author
Ibáñez, Borja
author
Ugalde, Alejandro P
author
López-Otín, Carlos
funder
Unión Europea. Comisión Europea
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Fundación ProCNIC
funder
Comunidad de Madrid (España)
funder
Fundación Cajastur
funder
Instituto de Salud Carlos III
funder
Centro de Investigación Biomedica en Red - CIBER
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Progeria Research Foundation
2019-02-07T11:31:05Z
2019-02-07T11:31:05Z
2018-10
PLoS Biol. 2018; 16(10):e2006247
1545-7885
http://hdl.handle.net/20.500.12105/7138
30346946
10.1371/journal.pbio.2006247
1545-7885
PLoS biology
Different microRNAs (miRNAs), including miR-29 family, may play a role in the development of heart failure (HF), but the underlying molecular mechanisms in HF pathogenesis remain unclear. We aimed at characterizing mice deficient in miR-29 in order to address the functional relevance of this family of miRNAs in the cardiovascular system and its contribution to heart disease. In this work, we show that mice deficient in miR-29a/b1 develop vascular remodeling and systemic hypertension, as well as HF with preserved ejection fraction (HFpEF) characterized by myocardial fibrosis, diastolic dysfunction, and pulmonary congestion, and die prematurely. We also found evidence that the absence of miR-29 triggers the up-regulation of its target, the master metabolic regulator PGC1α, which in turn generates profound alterations in mitochondrial biogenesis, leading to a pathological accumulation of small mitochondria in mutant animals that contribute to cardiac disease. Notably, we demonstrate that systemic hypertension and HFpEF caused by miR-29 deficiency can be rescued by PGC1α haploinsufficiency, which reduces cardiac mitochondrial accumulation and extends longevity of miR-29-mutant mice. In addition, PGC1α is overexpressed in hearts from patients with HF. Collectively, our findings demonstrate the in vivo role of miR-29 in cardiovascular homeostasis and unveil a novel miR-29/PGC1α regulatory circuitry of functional relevance for cell metabolism under normal and pathological conditions.
eng
The microRNA-29/PGC1α regulatory axis is critical for metabolic control of cardiac function
journal article
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
URL
https://repisalud.isciii.es/bitstreams/4deb8757-c31e-468d-9586-57724a6a5b59/download
File
MD5
ad3d097896301d9aebc22f143ef65f36
3706460
application/pdf
TheMicroRNA-29-PGC1alphaRegulatory_2018.pdf
URL
https://repisalud.isciii.es/bitstreams/a6e3ca39-4685-49c0-b0bd-0819d0ece5c9/download
File
MD5
ee896a2e9c0fc0b48855380cbcc95a9d
1331664
image/tiff
pbio.2006247.s011.TIF
URL
https://repisalud.isciii.es/bitstreams/3d941f2e-d4b7-4a79-864a-42fb061ac103/download
File
MD5
a2a02140272eab755c207380e030ade3
3268522
image/tiff
pbio.2006247.s010.TIF
URL
https://repisalud.isciii.es/bitstreams/722cca73-cd41-4f72-ac58-c2757683e365/download
File
MD5
90cbafb86046123f77e5f57eb5e9cb51
586048
image/tiff
pbio.2006247.s009.TIF
URL
https://repisalud.isciii.es/bitstreams/1276ea10-4521-49d4-82c9-c374cdaf4568/download
File
MD5
630c4f406b72623ae31522cb0522f527
513312
image/tiff
pbio.2006247.s008.TIF
URL
https://repisalud.isciii.es/bitstreams/b9c1f682-217f-4919-ade1-c684652beabb/download
File
MD5
a84ab10bf02acb9a19d79fc0b7e5cb27
1124430
image/tiff
pbio.2006247.s007.TIF
URL
https://repisalud.isciii.es/bitstreams/3196a888-bdb9-4edb-b9b0-8f8a839bf00c/download
File
MD5
5a09db98c1017014b9d531f2d4a550cf
431580
image/tiff
pbio.2006247.s006.TIF
URL
https://repisalud.isciii.es/bitstreams/aeeca8c5-3a41-4134-b987-1df71db63925/download
File
MD5
abd5029903f3b90eb423a7610e2ed41c
899926
image/tiff
pbio.2006247.s005.TIF
URL
https://repisalud.isciii.es/bitstreams/9aacce0d-9b66-40c5-a3c6-37a5d78184dd/download
File
MD5
cc9ada7fd5b2ec731b0f3c3cd94c3d4c
908010
image/tiff
pbio.2006247.s004.TIF
URL
https://repisalud.isciii.es/bitstreams/484518b4-c788-4946-81a6-d75a5531928e/download
File
MD5
00b58ec2cec5a92af1d81d04c1aa4aba
577172
image/tiff
pbio.2006247.s003.TIF
URL
https://repisalud.isciii.es/bitstreams/80a68f57-16e1-4158-8736-455557000faf/download
File
MD5
801d7993134fa667b2299c05f441a293
2214750
image/tiff
pbio.2006247.s002.TIF
URL
https://repisalud.isciii.es/bitstreams/5d2bda9a-2b8a-430f-ae73-9327b0b20c78/download
File
MD5
ec71911245996869f6bd6f803efe22d3
1161550
image/tiff
pbio.2006247.s001.TIF
URL
https://repisalud.isciii.es/bitstreams/e0dc44e6-0532-4607-b174-4d0f1ba2f18e/download
File
MD5
14c222723b5177f72d7ae664450f210d
254038
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
pbio.2006247.s024.xlsx
URL
https://repisalud.isciii.es/bitstreams/95dec3ad-e617-4391-ad0b-3692c33e946b/download
File
MD5
c394f85cca385b4ed540193c5c3b2a08
23919328
application/octet-stream
pbio.2006247.s023.mp4
URL
https://repisalud.isciii.es/bitstreams/80132646-72b7-471f-88c6-f956cfab73e7/download
File
MD5
d2002075d182b945b18e6f3a6307db25
11980
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
pbio.2006247.s021.xlsx
URL
https://repisalud.isciii.es/bitstreams/f806ac17-8d80-4408-9950-9e7a706491fd/download
File
MD5
e2d5191b26c3c7ccee5d6923d0a0bf18
15309
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
pbio.2006247.s022.xlsx
URL
https://repisalud.isciii.es/bitstreams/1fa47f21-3b9f-430e-b5d1-fdd4700d89b8/download
File
MD5
adcf75e70fe6c6831b4afddaebe76ceb
513933
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
pbio.2006247.s020.xlsx
URL
https://repisalud.isciii.es/bitstreams/672a2792-af0a-4f56-84d6-045b1e00b7fa/download
File
MD5
cd85a6e08c027fbdf893fc44e3e01648
505474
image/tiff
pbio.2006247.s019.TIF
URL
https://repisalud.isciii.es/bitstreams/a44efc53-4c2c-4d44-83eb-c5ebc23c57e6/download
File
MD5
ba01c968c161d36b91884813b05a4d94
310193
application/pdf
pbio.2006247.s017.pdf
URL
https://repisalud.isciii.es/bitstreams/3dcb3b42-f4f0-4fcc-8011-a33e40993104/download
File
MD5
715ec624ef01208237e1ac7978e9321a
442818
image/tiff
pbio.2006247.s018.TIF
URL
https://repisalud.isciii.es/bitstreams/3d5737df-ba39-4ff7-a5ca-d4522b8e9281/download
File
MD5
de347396dce06dc02f1f312eb6c04cd5
474184
image/tiff
pbio.2006247.s015.TIF
URL
https://repisalud.isciii.es/bitstreams/eca58a3d-c829-4fd6-8d15-ef835709048c/download
File
MD5
3cd9967d8b00683f41d6cdce94c02577
767524
image/tiff
pbio.2006247.s016.TIF
URL
https://repisalud.isciii.es/bitstreams/92f3808b-406d-4c71-ba06-aa172ef73d69/download
File
MD5
db18f7d171a9e70dbe4c0479d2633eb8
492408
image/tiff
pbio.2006247.s014.TIF
URL
https://repisalud.isciii.es/bitstreams/ae7902f9-95a8-403b-b24c-281e393d8ef6/download
File
MD5
9ce5bfbaebb3cd8173a3289fe88ab657
814190
image/tiff
pbio.2006247.s013.TIF
URL
https://repisalud.isciii.es/bitstreams/7a49e5b8-f3ed-4948-ad65-9c7dc3448618/download
File
MD5
5320b1f257639410df84e8cb6f6b411f
494668
image/tiff
pbio.2006247.s012.TIF
URL
https://repisalud.isciii.es/bitstreams/f82c523f-77da-4d02-80d0-ade1e0affd3f/download
File
MD5
9d42249d28e098c2118f1e611b46d5bb
96418
text/plain
TheMicroRNA-29-PGC1alphaRegulatory_2018.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/75d477cc-db2e-4f40-8ff0-9d8cf4f9ea81/download
File
MD5
9338c669a6f34ee59796c79db7aca162
6470
text/plain
pbio.2006247.s017.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/4455ac29-2c61-4cf1-80e8-3bd73dab561a/download
File
MD5
b6f8089c158a7bdeb227026d6bb97196
100196
text/plain
pbio.2006247.s024.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/d225c25b-9d3a-4471-becc-0423180cf991/download
File
MD5
ab5a40eaabd582ee026cfa69abbd595b
1775
text/plain
pbio.2006247.s021.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/9fe00ff4-c533-416a-bbe0-79da3e2cb282/download
File
MD5
4faee35dd4c4641c24bf8866e4ae8093
8009
text/plain
pbio.2006247.s022.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/73ccfbcc-22f5-4270-a3dd-8ec4d37ad525/download
File
MD5
e76ede4aa212143541ccc1f39349811d
100000
text/plain
pbio.2006247.s020.xlsx.txt