Arterial calcification in diabetes mellitus: Preclinical models and translational implications

John N. Stabley, Dwight A. Towler

Research output: Contribution to journalReview article

34 Scopus citations

Abstract

Diabetes mellitus increasingly afflicts our aging and dysmetabolic population. Type 2 diabetes mellitus and the antecedent metabolic syndrome represent the vast majority of the disease burden - increasingly prevalent in children and older adults. However, type 1 diabetes mellitus is also advancing in preadolescent children. As such, a crushing wave of cardiometabolic disease burden now faces our society. Arteriosclerotic calcification is increased in metabolic syndrome, type 2 diabetes mellitus, and type 1 diabetes mellitus - impairing conduit vessel compliance and function, thereby increasing the risk for dementia, stroke, heart attack, limb ischemia, renal insufficiency, and lower extremity amputation. Preclinical models of these dysmetabolic settings have provided insights into the pathobiology of arterial calcification. Osteochondrogenic morphogens in the BMP-Wnt signaling relay and transcriptional regulatory programs driven by Msx and Runx gene families are entrained to innate immune responses - responses activated by the dysmetabolic state - to direct arterial matrix deposition and mineralization. Recent studies implicate the endothelial-mesenchymal transition in contributing to the phenotypic drift of mineralizing vascular progenitors. In this brief overview, we discuss preclinical disease models that provide mechanistic insights - and point to challenges and opportunities to translate these insights into new therapeutic strategies for our patients afflicted with diabetes mellitus and its arteriosclerotic complications.

Original languageEnglish (US)
Pages (from-to)205-217
Number of pages13
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume37
Issue number2
DOIs
StatePublished - Feb 1 2017

    Fingerprint

Keywords

  • amputation
  • arteriosclerosis
  • dementia
  • diabetes mellitus
  • vascular calcification

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this