Aortic Aneurysms, Chronic Kidney Disease and Metalloproteinases

Biomolecules. 2021 Jan 30;11(2):194. doi: 10.3390/biom11020194.


Metalloproteinases (MPs) are proteolytic enzymes involved in extracellular matrix deposition, regulation of cellular signals of inflammation, proliferation, and apoptosis. Metalloproteinases are classified into three families: Matrix-MPs (MMPs), A-Disintegrin-and-Metalloprotease (ADAMs), and the A-Disintegrin-and-Metalloproteinase-with-Thrombospondin-1-like-Domains (ADAMTS). Previous studies showed that MPs are involved in the development of aortic aneurysms (AA) and, concomitantly, in the onset of chronic kidney disease (CKD). CKD has been, per se, associated with an increased risk for AA. The aim of this review is to examine the pathways that may associate MPs with CKD and AA. Several MMPs, such as MMP-2, -8, -9, and TIMP-1 have been shown to damage the AA wall and to have a toxic effect on renal tubular cells, leading to fibrosis. Similarly, ADAM10 and 17 have been shown to degrade collagen in the AA wall and to worsen kidney function via pro-inflammatory stimuli, the impairment of the Renin-Angiotensin-Aldosterone System, and the degradation of structural proteins. Moreover, MMP-2 and -9 inhibitors reduced aneurysm growth and albuminuria in experimental and human studies. It would be important, in the future, to expand research on MPs from both a prognostic, namely, to refine risk stratification in CKD patients, and a predictive perspective, likely to improve prognosis in response to targeted treatments.

Keywords: MPs; aneurysm expansion; cardiovascular risk; eGFR; end-stage kidney disease; extracellular matrix; proteinuria; renal tubular injury.

Publication types

  • Review

MeSH terms

  • Aneurysm / physiopathology
  • Animals
  • Aortic Aneurysm / complications
  • Aortic Aneurysm / enzymology
  • Aortic Aneurysm / physiopathology*
  • Apoptosis
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Extracellular Matrix / metabolism
  • Fibrosis
  • Glomerular Filtration Rate*
  • Humans
  • Inflammation
  • Kidney Failure, Chronic / physiopathology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 8 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Metalloproteases / metabolism*
  • Prognosis
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / enzymology
  • Renal Insufficiency, Chronic / physiopathology*
  • Renin-Angiotensin System
  • Risk
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism


  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Metalloproteases
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP8 protein, human
  • Matrix Metalloproteinase 8
  • MMP9 protein, human
  • Matrix Metalloproteinase 9