Abnormal microvascular architecture, fibrosis, and pericyte characteristics in the calf muscle of peripheral artery disease patients with claudication and critical limb ischemia

Constance J. Mietus, Timothy J. Lackner, Petros S. Karvelis, Gregory T. Willcockson, Christina M. Shields, Nicholas G. Lambert, Panagiotis Koutakis, Matthew A. Fuglestad, Hernan Hernandez, Gleb R. Haynatzki, Julian K.S. Kim, Holly K. Despiegelaere, Iraklis I. Pipinos, George P. Casale

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Work from our laboratory documents pathological events, including myofiber oxidative damage and degeneration, myofibrosis, micro-vessel (diameter = 50–150 µm) remodeling, and collagenous investment of terminal micro-vessels (diameter ≤ 15 µm) in the calf muscle of patients with Peripheral Artery Disease (PAD). In this study, we evaluate the hypothesis that the vascular pathology associated with the legs of PAD patients encompasses pathologic changes to the smallest micro-vessels in calf muscle. Biopsies were collected from the calf muscle of control subjects and patients with Fontaine Stage II and Stage IV PAD. Slide specimens were evaluated by Quantitative Multi-Spectral and Fluorescence Microscopy. Inter-myofiber collagen, stained with Masson Trichrome (MT), was increased in Stage II patients, and more substantially in Stage IV patients in association with collagenous thickening of terminal micro-vessel walls. Evaluation of the Basement Membrane (BM) of these vessels reveals increased thickness in Stage II patients, and increased thickness, diameter, and Collagen I deposition in Stage IV patients. Coverage of these micro-vessels with pericytes, key contributors to fibrosis and BM remodeling, was increased in Stage II patients, and was greatest in Stage IV patients. Vascular pathology of the legs of PAD patients extends beyond atherosclerotic main inflow arteries and affects the entire vascular tree—including the smallest micro-vessels.

Original languageEnglish (US)
Article number2575
Pages (from-to)1-20
Number of pages20
JournalJournal of Clinical Medicine
Volume9
Issue number8
DOIs
StatePublished - Aug 2020

Keywords

  • Basement membrane thickening
  • Fibrosis
  • Microvascular pathology
  • αSMA+ pericytes

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Abnormal microvascular architecture, fibrosis, and pericyte characteristics in the calf muscle of peripheral artery disease patients with claudication and critical limb ischemia'. Together they form a unique fingerprint.

Cite this