Journal Article

Versican is differentially regulated in the adventitial and medial layers of human vein grafts

Pesce, Maurizio, Soncini, Monica, Kenagy, Richard D., Majesky, Mark W., Sobel, Michael, Kikuchi, Shinsuke, Longchamp, Alban, Deglise, Sébastien, Schmidt, Tannin A., Ruiter, Matthijs S., Fiore, Gianfranco B., Haefliger, Jacques-Antoine, Wight, Thomas N., Piola, Marco, Evanko, Steve P.

2018

Overview

Changes in extracellular matrix proteins may contribute significantly to the adaptation of vein grafts to the arterial circulation. We examined the production and distribution of versican and hyaluronan in intact human vein rings cultured ex vivo, veins perfused ex vivo, and cultured venous adventitial and smooth muscle cells. Immunohistochemistry revealed higher levels of versican in the intima/media compared to the adventitia, and no differences in hyaluronan. In the vasa vasorum, versican and hyaluronan associated with CD34+ progenitor cells. Culturing the vein rings for 14 days revealed increased versican immunostaining of 30-40% in all layers, with no changes in hyaluronan. Changes in versican accumulation appear to result from increased synthesis in the intima/media and decreased degradation in the adventitia as versican transcripts were increased in the intima/media, but unchanged in the adventitia, and versikine (the ADAMTS-mediated cleavage product of versican) was increased in the intima/media, but decreased in the adventitia. In perfused human veins, versican was specifically increased in the intima/media in the presence of venous pressure, but not with arterial pressure. Unexpectedly, cultured adventitial cells express and accumulate more versican and hyaluronan than smooth muscle cells. These data demonstrate a differential regulation of versican and hyaluronan in human venous adventitia vs. intima/media and suggest distinct functions for these extracellular matrix macromolecules in these venous wall compartments during the adaptive response of vein grafts to the arterial circulation.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adventitia - metabolism / Antigens, CD34 - metabolism / Arterial Pressure - physiology / Atherosclerosis / Biology / Biology and Life Sciences / Blood pressure / CD34 antigen / Cell growth / Cells (biology) / Cells, Cultured / Coronary vessels / Extracellular matrix / Grafting / Grafts / Hospitals / Humans / Hyaluronic acid / Hyaluronic Acid - metabolism / Immunohistochemistry / Kinases / Macromolecules / Media / Medicine and Health Sciences / Methods / Muscles / Myocytes, Smooth Muscle - metabolism / Physical Sciences / Physiological aspects / Progenitor cells / Proteins / Research and Analysis Methods / Saphenous Vein - cytology / Saphenous Vein - metabolism / Smooth muscle / Stem cells / Stem Cells - metabolism / Tissue Culture Techniques / Tissue engineering / Tunica Intima - cytology / Tunica Intima - metabolism / Tunica Media - cytology / Tunica Media - metabolism / Vasa Vasorum - cytology / Vasa Vasorum - metabolism / Vascular surgery / Veins / Veins & arteries / Veins - cytology / Veins - metabolism / Veins - transplantation / Versican / Versicans - genetics / Versicans - metabolism