Regulation of angiogenesis by microRNAs in cardiovascular diseases

Kir, Devika; Schnettler, Erica; Modi, Shrey; Ramakrishnan, Sundaram

doi:10.1007/s10456-018-9632-7

Cited by 81 publications

(67 citation statements)

References 84 publications

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“…MicroRNAs (miRNAs) are evolutionarily conserved, small, single-stranded, noncoding RNAs that are capable of suppressing target gene expression and have emerged as important regulators of the angiogenic response in a variety of pathophysiological processes (18)(19)(20). For example, miRNAs such as miR-17-92, -217, -34, and -26a are able to confer antiangiogenic effects, whereas miRNAs such as miR-7-5p, -18a, -31, -155, -201, and -424 can generate proangiogenic responses (21)(22)(23)(24)(25)(26)(27)(28)(29).…”

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confidence: 99%

MicroRNA‐135a‐3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells

Icli

Ozdemir

et al. 2019

FASEB j.

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Angiogenesis is a critical process in repair of tissue injury that is regulated by a delicate balance between pro‐ and antiangiogenic factors. In disease states associated with impaired angiogenesis, we identified that miR‐135a‐3p is rapidly induced and serves as an antiangiogenic microRNA (miRNA) by targeting endothelial cell (EC) p38 signaling in vitro and in vivo. MiR‐135a‐3p overexpression significantly inhibited EC proliferation, migration, and network tube formation in matrigel, whereas miR‐135‐3p neutralization had the opposite effects. Mechanistic studies using transcriptomic profiling, bioinformatics, 3′‐UTR reporter and miRNA ribonucleoprotein complex ‐immunoprecipitation assays, and small interfering RNA dependency studies revealed that miR‐135a‐3p inhibits the p38 signaling pathway in ECs by targeting huntingtin‐interacting protein 1 (HIP1). Local delivery of miR‐135a‐3p inhibitors to wounds of diabetic db/db mice markedly increased angiogenesis, granulation tissue thickness, and wound closure rates, whereas local delivery of miR‐135a‐3p mimics impaired these effects. Finally, through gain‐ and loss‐of‐function studies in human skin organoids as a model of tissue injury, we demonstrated that miR‐135a‐3p potently modulated p38 signaling and angiogenesis in response to VEGF stimulation by targeting HIP1. These findings establish miR‐135a‐3p as a pivotal regulator of pathophysiological angiogenesis and tissue repair by targeting a VEGF‐HIP1‐p38K signaling axis, providing new targets for angiogenic therapy to promote tissue repair.—Icli, B., Wu, W., Ozdemir, D., Li, H., Haemmig, S., Liu, X., Giatsidis, G., Cheng, H. S., Avci, S. N., Kurt, M., Lee, N., Guimaraes, R. B., Manica, A., Marchini, J. F., Rynning, S. E., Risnes, I., Hollan, I., Croce, K., Orgill, D. P., Feinberg, M. W. MicroRNA‐135a‐3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells. FASEB J. 33, 5599–5614 (2019). http://www.fasebj.org

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confidence: 99%

MicroRNA‐135a‐3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells

Icli

Ozdemir

et al. 2019

FASEB j.

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“…triggered by a multitude of signals and guidance cues leading to proper endothelial cell path finding [39][40][41], the precise role of zinc and zinc transporters in regulating angiogenesis remains poorly understood. In summary, our results support a model in which Slc39a5-mediated zinc homeostasis is essential for the normal development of venous angiogenesis, as loss of Slc39a5 results in systemic zinc accumulation, delayed CVP sprouting and impaired endothelial cell migration (figure 6).…”

Section: Discussionmentioning

confidence: 99%

Slc39a5-mediated zinc homeostasis plays an essential role in venous angiogenesis in zebrafish

Xia

Lian

et al. 2020

Open Biol.

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Angiogenesis is a precise process mediated by a variety of signals and the environmental niche. Although the essential trace element zinc and its homeostasis are essential for maintaining proper cellular functions, whether zinc plays a role in angiogenesis is currently unknown. Using zebrafish embryos as a model system, we found that zinc treatment significantly increased the expression of the slc39a5 gene, which encodes the zinc transporter Slc39a5. Moreover, knocking down slc39a5 expression using either a morpholino or CRISPR/Cas9-mediated gene editing led to cardiac ischaemia and an accumulation of red blood cells in the caudal vein plexus (CVP), as well as delayed venous sprouting and fewer vascular loops in the CVP region during early development. Further analysis revealed significantly reduced proliferation and delayed cell migration in the caudal vein of slc39a5 morphants. At the mechanistic level, we found increased levels of systemic zinc in slc39a5 -deficient embryos, and chelating zinc restored CVP development. In addition, we found that zinc overload in wild-type embryos leads to impaired CVP formation. Taken together, these results indicate that Slc39a5 plays a critical role in endothelial sprouting and migration in venous angiogenesis by regulating zinc homeostasis.

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“…Ongoing researches on preconditioning and genetic manipulations of MSCs are needed to enhance angiocrine capacity governed by growth factors, microvesicles, microRNAs, long noncoding RNAs (lncRNAs), etc. [128,129]. Finding the route of cell delivery, the optimum dose, the excellent cell source, and transplantation time are factors that still require to be addressed so as to achieve the aim of comprehensive cardiac regeneration.…”

Section: The Application Of Mscs and Secretome In Ischemic Cardiac DImentioning

confidence: 99%

The Angiogenic Paracrine Potential of Mesenchymal Stem Cells

Rezaie¹,

Heidarzadeh²,

Hassanpour³

et al. 2020

Update on Mesenchymal and Induced Pluripotent Stem Cells

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Tissue engineering and regenerative medicine are branches of biomedical sciences that facilitate the use of cells and biocompatible scaffolds in favor of tissue restoration. In this regard, restoration and maintenance of angiogenesis and blood supplementation could be an effective strategy for injured tissue removal, accelerating healing rate, and successful transplantation of cells and scaffolds into target sites. It has been elucidated that mesenchymal stem cells have the potency to promote angiogenesis via paracrine activity and trans-differentiation into the endothelial lineage. In this chapter, we highlighted the paracrine property of mesenchymal stem cells to modulate angiogenesis in the target tissues.

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Regulation of angiogenesis by microRNAs in cardiovascular diseases

Cited by 81 publications

References 84 publications

MicroRNA‐135a‐3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells

MicroRNA‐135a‐3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells

Slc39a5-mediated zinc homeostasis plays an essential role in venous angiogenesis in zebrafish

The Angiogenic Paracrine Potential of Mesenchymal Stem Cells

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