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08:43

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Pathological Insights Into the Relationship Between Medial and Intimal Calcification in Lower Extremity Artery

Tsukasa Kato1, Sho Torii2, Manabu Shiozaki2

  • 1Department of Cardiology, Akita University School of Medicine, Akita, Japan; Department of Cardiology, Tokai University School of Medicine, Isehara, Japan.

JACC. Advances
|June 11, 2026
PubMed

Insights

Medial artery calcification (MAC) and intimal artery calcification (IAC) are distinct pathologies in lower extremity artery disease. Advanced MAC correlates with less intimal plaque, potentially explaining treatment resistance in below-knee arteries.

Area of Science:

  • Vascular biology and pathology
  • Arterial calcification mechanisms
  • Lower extremity artery disease

Background:

  • Medial artery calcification (MAC) is a key feature of lower extremity artery disease.
  • The distribution and relationship of MAC with intimal artery calcification (IAC) are not well understood.
  • Current imaging has limitations in differentiating MAC and IAC.

Purpose of the Study:

  • To characterize the histopathological distribution and morphology of MAC.
  • To determine the spatial relationship between MAC and intimal atherosclerotic plaque.

Main Methods:

  • Systematic histopathological analysis of 3,566 cross-sections from 125 arterial segments in 58 patients.
  • Quantification of calcification by circumferential arc.
  • Classification of plaque morphology using modified AHA criteria.

Main Results:

  • MAC was highly prevalent (91.2%) and more extensive below-the-knee.
  • Medial bone formation (16.0%) associated with advanced MAC.
  • MAC and IAC showed inverse correlation (r = -0.47) and spatial segregation.

Conclusions:

  • MAC and IAC are spatially distinct calcific pathologies with an inverse relationship.
  • Advanced MAC may inhibit intimal atherosclerotic plaque development.
  • This may explain poor response to endovascular therapy in below-knee lesions.
Abstract

Keywords:
bone formationchronic limb-threatening ischemiaintimal artery calcificationlower extremity artery diseasemedial artery calcification

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