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See detailMicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy.
Halkein, Julie; Tabruyn, Sebastien P.; Ricke-Hoch, Melanie et al

in Journal of Clinical Investigation (2013), 123(5), 2143-54

Peripartum cardiomyopathy (PPCM) is a life-threatening pregnancy-associated cardiomyopathy in previously healthy women. Although PPCM is driven in part by the 16-kDa N-terminal prolactin fragment (16K PRL ... [more ▼]

Peripartum cardiomyopathy (PPCM) is a life-threatening pregnancy-associated cardiomyopathy in previously healthy women. Although PPCM is driven in part by the 16-kDa N-terminal prolactin fragment (16K PRL), the underlying molecular mechanisms are poorly understood. We found that 16K PRL induced microRNA-146a (miR-146a) expression in ECs, which attenuated angiogenesis through downregulation of NRAS. 16K PRL stimulated the release of miR-146a-loaded exosomes from ECs. The exosomes were absorbed by cardiomyocytes, increasing miR-146a levels, which resulted in a subsequent decrease in metabolic activity and decreased expression of Erbb4, Notch1, and Irak1. Mice with cardiomyocyte-restricted Stat3 knockout (CKO mice) exhibited a PPCM-like phenotype and displayed increased cardiac miR-146a expression with coincident downregulation of Erbb4, Nras, Notch1, and Irak1. Blocking miR-146a with locked nucleic acids or antago-miRs attenuated PPCM in CKO mice without interrupting full-length prolactin signaling, as indicated by normal nursing activities. Finally, miR-146a was elevated in the plasma and hearts of PPCM patients, but not in patients with dilated cardiomyopathy. These results demonstrate that miR-146a is a downstream-mediator of 16K PRL that could potentially serve as a biomarker and therapeutic target for PPCM. [less ▲]

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See detailMicroRNA-146a, a downstream effector of 16K prolactin, is a therapeutic target and a specific biomarker for peripartum cardiomyopathy
Halkein, Julie ULg; Tabruyn, Sébastien ULg; Haghikia, Arash et al

Poster (2012, May 19)

Detailed reference viewed: 12 (4 ULg)
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See detailMicroRNA-146a is a causative factor and a specific biomarker for peripartum cardiomyopathy
Halkein, Julie ULg; Tabruyn, Sébastien ULg; Haghikia, Arash et al

Poster (2012, April)

Detailed reference viewed: 10 (1 ULg)
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See detailMiR-146a an angiostatic miRNA elevated in peripartum cardiomyopathy
Halkein, Julie ULg; Tabruyn, Sébastien ULg; Haghikia, Arash et al

Poster (2012, January)

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See detailMir-146a : A new angiostatic miRNA with tumor-suppressive properties
Halkein, Julie ULg; Castermans, Karolien; Malvaux, Ludovic et al

Poster (2011, March)

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See detailMiR-146a an angiostatic miRNA elevated in peripartum cardiomyopathy
Halkein, Julie ULg; Castermans, Karolien; Malvaux, Ludovic et al

Poster (2011, March)

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See detailMiR-146a an angiostatic miRNA elevated in peripartum cardiomyopathy
Halkein, Julie ULg; Castermans, Karolien; Malvaux, Ludovic et al

Poster (2011, February)

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See detailMiR-146a: an angiostatic miRNA with tumor-suppressive properties
Halkein, Julie ULg; Bovy, Nicolas ULg; Castermans, Karolien et al

Poster (2011, February)

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See detailmicroRNA-21 Exhibits Anti-Angiogenic Function by Targeting RhoB Expression in Endothelial Cells
Sabatel, Céline; Malvaux, Ludovic; Bovy, Nicolas ULg et al

Poster (2011, February)

Detailed reference viewed: 5 (1 ULg)
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See detailMiR-146a an angiostatic miRNA elevated in peripartum cardiomyopathy
Halkein, Julie ULg; Castermans, Karolien; Malvaux, Ludovic et al

Poster (2011, January)

Detailed reference viewed: 7 (1 ULg)
Peer Reviewed
See detailMir-146a : A new angiostatic miRNA with tumor-suppressive properties
Halkein, Julie ULg; Castermans, Karolien; Malvaux, Ludovic et al

Poster (2010, October)

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See detailInvolvement of miR-125b in in vitro and in vivo angiogenesis
Malvaux, Ludovic; Pendeville, Hélène; Sabatel, Céline et al

Poster (2010, May 21)

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See detailStudy of the role of miR-21 in the regulation of angiogenesis
Sabatel, Céline; Malvaux, Ludovic; Bovy, Nicolas ULg et al

Poster (2010, May)

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See detailInvolvement of miR-125b in in vitro and in vivo angiogenesis
Malvaux, Ludovic; Pendeville, Hélène; Sabatel, Céline et al

Poster (2010, March)

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See detailStudy of the role of miR-21 in the regulation of angiogenesis
Sabatel, Céline; Malvaux, Ludovic; Bovy, Nicolas ULg et al

Poster (2010, March)

Detailed reference viewed: 7 (1 ULg)
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See detailEffect of ADAMTS-2, a metalloproteinase containing a disintegrin domain and thrombospondin type I repeats, during angiogenesis in vitro and in vivo
Dubail, Johanne ULg; Kesteloot, Frédéric ULg; Motte, Patrick ULg et al

in Angiogenesis (2004), 7(2), 172

Formation of new blood vessels (angiogenesis) is a key step during the development of various pathologies, including cancer. Enzymes of the ADAMTS family are closely related to MMPs and ADAMs. They ... [more ▼]

Formation of new blood vessels (angiogenesis) is a key step during the development of various pathologies, including cancer. Enzymes of the ADAMTS family are closely related to MMPs and ADAMs. They further contain specific domains, such as the ‘‘Thrombospondin type I’’ (TSP1) repeats, that are able to strongly repress angiogenesis, as described for thrombospondin-1 and -2, and for ADAMTS-1 and -8. The primary function of ADAMTS-2 is to process collagen type I, II and III precursors into mature molecules by excising the aminopropeptide. We further hypothesized that it could modulate angiogenesis through its TSP1 repeats. This hypothesis was investigated using different in vitro experimental models of angiogenesis. Recombinant ADAMTS-2 induced morphological changes in human umbilical vein endothelial cells (HUVEC) and human microvessel endothelial cells (HMEC), and significantly reduced their proliferation, attachment and spreading. Similar effects were observed when using inactive ADAMTS-2 mutated at the Zn2+-binding catalytic site. ADAMTS-2 did not alter the initial steps of formation of capillary-like structures by HUVEC in vitro. However, these structures appeared much less stable and were more rapidly disrupted in presence of ADAMTS-2 than in control conditions. ADAMTS-2 was also tested in an ex vivo angiogenesis model using aortic rings from rats and mice, wild type or KO for ADAMTS-2. Outgrowth of capillaries was slightly increased from aortas of ADAMTS-2 KO mice (TS2-/-) as compared to aortas from control animals (TS2+/+), while addition of full size recombinant ADAMTS-2 reduced the formation of capillary structures from rat aortas, suggesting its anti-angiogenic activity. Choroidal neovascularization induced in TS2+/+ or TS2-/- mice by LASER burns was used as in vivo model to confirm the in vitro and ex vivo results. Several genes involved in the healing and angiogenesis processes (fibrillar collagens, VEGF, TGF-beta and CTGF) were not differently regulated in TS2+/+ and TS2-/- mice at 5 days. [less ▲]

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