Osteogenic regulation of vascular calcification: An early perspective

Radhika Vattikuti, Dwight A. Towler

Research output: Contribution to journalShort survey

290 Citations (Scopus)

Abstract

Cardiovascular calcification is a common consequence of aging, diabetes, hypercholesterolemia, mechanically abnormal valve function, and chronic renal insufficiency. Although vascular calcification may appear to be a uniform response to vascular insult, it is a heterogenous disorder, with overlapping yet distinct mechanisms of initiation and progression. A minimum of four histoanatomic variants-atherosclerotic (fibrotic) calcification, cardiac valve calcification, medial artery calcification, and vascular calciphylaxis-arise in response to metabolic, mechanical, infectious, and inflammatory injuries. Common to the first three variants is a variable degree of vascular infiltration by T cells and macrophages. Once thought benign, the deleterious clinical consequences of calcific vasculopathy are now becoming clear; stroke, amputation, ischemic heart disease, and increased mortality are portended by the anatomy and extent of calcific vasculopathy. Along with dystrophic calcium deposition in dying cells and lipoprotein deposits, active endochondral and intramembranous (nonendochondral) ossification processes contribute to vascular calcium load. Thus vascular calcification is subject to regulation by osteotropic hormones and skeletal morphogens in addition to key inhibitors of passive tissue mineralization. In response to oxidized lipids, inflammation, and mechanical injury, the microvascular smooth muscle cell becomes activated. Orthotopically, proliferating stromal myofibroblasts provide osteoprogenitors for skeletal growth and fracture repair; however, in valves and arteries, vascular myofibroblasts contribute to cardiovascular ossification. Current data suggest that paracrine signals are provided by bone morphogenetic protein-2, Wnts, parathyroid hormone-related polypeptide, osteopontin, osteoprotegerin, and matrix Gla protein, all entrained to endocrine, metabolic, inflammatory, and mechanical cues. In end-stage renal disease, a "perfect storm" of vascular calcification often occurs, with hyperglycemia, hyperphosphatemia, hypercholesterolemia, hypertension, parathyroid hormone resistance, and iatrogenic calcitriol excess contributing to severe calcific vasculopathy. This brief review recounts emerging themes in the pathobiology of vascular calcification and highlights some fundamental deficiencies in our understanding of vascular endocrinology and metabolism that are immediately relevant to human health and health care.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume286
Issue number5 49-5
DOIs
StatePublished - May 1 2004

Fingerprint

Vascular Calcification
Parathyroid Hormone
Blood Vessels
Endocrinology
Calcium
Osteoprotegerin
Bone Morphogenetic Protein 2
Osteopontin
T-cells
Calcitriol
Macrophages
Medical problems
Health care
Infiltration
Metabolism
Myofibroblasts
Lipoproteins
Muscle
Hypercholesterolemia
Repair

Keywords

  • Adipocyte
  • Bone morphogenetic protein-2
  • Cholesterol
  • Chondrocyte
  • Diabetes
  • Macrophage
  • Osteoblast
  • Osteopontin
  • Parathyroid hormone
  • Parathyroid hormone-related polypeptide
  • Pericyte
  • T cell
  • Vitamin D

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Osteogenic regulation of vascular calcification : An early perspective. / Vattikuti, Radhika; Towler, Dwight A.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 286, No. 5 49-5, 01.05.2004.

Research output: Contribution to journalShort survey

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