Mechanisms of Arterial Calcification: The Role of Matrix Vesicles

Eur J Vasc Endovasc Surg. 2018 Mar;55(3):425-432. doi: 10.1016/j.ejvs.2017.12.009. Epub 2018 Jan 20.

Abstract

Vascular calcification is related to vascular diseases, for example, atherosclerosis, and its comorbidities, such as diabetes and chronic kidney disease. In each condition, a distinctive histological pattern can be recognised that may influence technical choices, possible intra-operative complications, and procedure outcomes, no matter if the intervention is performed by open or endovascular means. This review considers the classification and initiating mechanisms of vascular calcification. Dystrophic and metastatic calcifications, Monckeberg's calcification, and genetic forms are firstly outlined, followed by their alleged initiation mechanisms; these include (a) ineffective macrophage efferocytosis; (b) ectopic osteogenesis driven by modified resident or circulating osteoprogenitors. As in physiological bio-mineralisation, active calcification starts with the deposition of cell derived matrix vesicles into the extracellular matrix. To substantiate this belief, an in depth ultra-structural documentation of hydroxyapatite crystal deposition on such vesicles is provided in an ex-vivo human vascular cell model. Revealing the vesicle composition and phenotype in normal and pathological vascular conditions will be essential for the development of new therapeutic strategies, in order to prevent and treat vascular calcification.

Keywords: Atherosclerosis; Electron microscopy; Matrix vesicles; Vascular calcification; Vascular stem cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Arteries / metabolism
  • Arteries / pathology*
  • Arteries / ultrastructure
  • Calcium Phosphates / metabolism
  • Cell Differentiation
  • Crystallization
  • Durapatite / metabolism
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology*
  • Extracellular Matrix / ultrastructure
  • Extracellular Vesicles / metabolism
  • Extracellular Vesicles / pathology*
  • Extracellular Vesicles / ultrastructure
  • Fibrosis
  • Humans
  • Monckeberg Medial Calcific Sclerosis / metabolism
  • Monckeberg Medial Calcific Sclerosis / pathology
  • Peripheral Arterial Disease / metabolism
  • Peripheral Arterial Disease / pathology*
  • Phenotype
  • Vascular Calcification / metabolism
  • Vascular Calcification / pathology*

Substances

  • Calcium Phosphates
  • Durapatite
  • calcium phosphate