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Targeting Wnt-Frizzled signaling in cardiovascular diseases

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Abstract

Wnts are secreted glycoproteins implicated in biological processes ranging from embryonic cardiac development to uncontrolled cell proliferation in diseased conditions. Cardiovascular disease is a major cause of morbidity and mortality worldwide. Phenotypic modulation of vascular smooth muscle cells, migration and proliferation in intimal layer and increased extracellular matrix production are some of the known hallmarks of cardiovascular pathologies. Heterogeneity associated with the binding of Wnts to their transmembrane receptors, Frizzled, and coreceptors low density lipoprotein-receptor-related protein is indeed intriguing. Nuclear-cytoplasmic shuttling of beta-catenin and activation of transcriptional factors, lymphoid enhancer factor and T cell activation factor leading to target gene activation has remained elusive. Our review highlights the emerging role of Wnt-Frizzled signaling in cardiovascular diseases. Overall, the pathway appears to be an attractive therapeutic target in identifying susceptible individuals at risk of developing restenosis/other vascular pathologies in the near future.

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Abbreviations

APC:

Adenomatous polyposis coli

β-cat:

Beta-catenin

CK:

Casein kinase

[Ca]i:

Intracellular calcium

CamK:

Calmodulin dependent protein kinase

DAG:

Diacyl glycerol

Dsh:

Dishevelled

Fzd:

Frizzled

GSK:

Glycogen synthase kinase

IP3 :

Inositol-tri-phosphate

LEF:

Lymphoid enhancer factor

LRP:

Low density-lipoprotein-receptor related protein

PKC:

Protein kinase C

PLC:

Phospholipase C

TCF:

T cell activation factor

Wnt:

Drosophila Wingless and mouse Int-1

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Acknowledgments

We have not received any payment/honoraria in the preparation of this manuscript from Government funding agencies or Corporate/Industrial sponsor. We apologise to colleagues in the Wnt/vascular field(s) whose work may not have been cited due to space reasons.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Krishna Medical Centre, 1, Rana Pratap Marg, Lucknow, 226001, Uttar Pradesh, India

    Saumya Pandey &  Chandravati

  2. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA

    Saumya Pandey

  3. Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, USA

    Saumya Pandey

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  1. Saumya Pandey
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  2. Chandravati
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Correspondence to Saumya Pandey.

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Pandey, S., Chandravati Targeting Wnt-Frizzled signaling in cardiovascular diseases. Mol Biol Rep 40, 6011–6018 (2013). https://doi.org/10.1007/s11033-013-2710-4

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