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Contribution of ADAM17 and related ADAMs in cardiovascular diseases

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Abstract

A disintegrin and metalloproteases (ADAMs) are key mediators of cell signaling by ectodomain shedding of various growth factors, cytokines, receptors and adhesion molecules at the cellular membrane. ADAMs regulate cell proliferation, cell growth, inflammation, and other regular cellular processes. ADAM17, the most extensively studied ADAM family member, is also known as tumor necrosis factor (TNF)-α converting enzyme (TACE). ADAMs-mediated shedding of cytokines such as TNF-α orchestrates immune system or inflammatory cascades and ADAMs-mediated shedding of growth factors causes cell growth or proliferation by transactivation of the growth factor receptors including epidermal growth factor receptor. Therefore, increased ADAMs-mediated shedding can induce inflammation, tissue remodeling and dysfunction associated with various cardiovascular diseases such as hypertension and atherosclerosis, and ADAMs can be a potential therapeutic target in these diseases. In this review, we focus on the role of ADAMs in cardiovascular pathophysiology and cardiovascular diseases. The main aim of this review is to stimulate new interest in this area by highlighting remarkable evidence.

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Funding

This work was supported by National Institute of Health grants, HL128324 (S.E.), HL133248 (S.E.), DK111042 (R.S. and S.E.), and NS109382 (S.E.).

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TK and SE proposed the idea and writing. KE and RS proof-read the article and performed critical revision in organization and discussion.

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Kawai, T., Elliott, K.J., Scalia, R. et al. Contribution of ADAM17 and related ADAMs in cardiovascular diseases. Cell. Mol. Life Sci. 78, 4161–4187 (2021). https://doi.org/10.1007/s00018-021-03779-w

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