Contribution of ADAM17 and related ADAMs in cardiovascular diseases

Cell Mol Life Sci. 2021 May;78(9):4161-4187. doi: 10.1007/s00018-021-03779-w. Epub 2021 Feb 11.


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.

Keywords: Angiotensin; Atherosclerosis; Endothelium; Heart disease; Hypertension; Inflammation; Signal transduction; Vascular biology.

Publication types

  • Review

MeSH terms

  • ADAM Proteins / metabolism*
  • ADAM17 Protein / metabolism*
  • Angiotensin II / metabolism
  • Animals
  • Aortic Aneurysm / metabolism
  • Aortic Aneurysm / pathology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology*
  • Cytokines / metabolism
  • Humans
  • Hypertension / metabolism
  • Hypertension / pathology
  • Signal Transduction


  • Cytokines
  • Angiotensin II
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human