A Novel Model of Tobacco Smoke–Mediated Aortic Injury

Amir F. Azarbal, Tana Repella, Eric Carlson, Elise C. Manalo, Braden Palanuk, Nasibeh Vatankhah, Keith Zientek, Douglas R. Keene, Wenri Zhang, Cherrie Z. Abraham, Gregory L. Moneta, Gregory J. Landry, Nabil J. Alkayed, Lynn Y. Sakai

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Tobacco smoke exposure is a major risk factor for aortic aneurysm development. However, the initial aortic response to tobacco smoke, preceding aneurysm formation, is not well understood. We sought to create a model to determine the effect of solubilized tobacco smoke (STS) on the thoracic and abdominal aorta of mice as well as on cultured human aortic smooth muscle cells (HASMCs). Methods: Tobacco smoke was solubilized and delivered to mice via implanted osmotic minipumps. Twenty male C57BL/6 mice received STS or vehicle infusion. The descending thoracic, suprarenal abdominal, and infrarenal abdominal segments of the aorta were assessed for elastic lamellar damage, smooth muscle cell phenotype, and infiltration of inflammatory cells. Cultured HASMCs grown in media containing STS were compared to cells grown in standard media in order to verify our in vivo findings. Results: Tobacco smoke solution caused significantly more breaks in the elastic lamellae of the thoracic and abdominal aorta compared to control solution (P<.0001) without inciting an inflammatory infiltrate. Elastin breaks occurred more frequently in the abdominal aorta than the thoracic aorta (P <.01). Exposure to STS-induced aortic microdissections and downregulation of α-smooth muscle actin (α-SMA) by vascular smooth muscle cells (VSMCs). Treatment of cultured HASMCs with STS confirmed the decrease in α-SMA expression. Conclusion: Delivery of STS via osmotic minipumps appears to be a promising model for investigating the early aortic response to tobacco smoke exposure. The initial effect of tobacco smoke exposure on the aorta is elastic lamellar damage and downregulation of (α-SMA) expression by VSMCs. Elastic lamellar damage occurs more frequently in the abdominal aorta than the thoracic aorta and does not seem to be mediated by the presence of macrophages or other inflammatory cells.

Original languageEnglish (US)
Pages (from-to)244-252
Number of pages9
JournalVascular and Endovascular Surgery
Volume56
Issue number3
DOIs
StatePublished - Apr 2022

Keywords

  • aortic aneurysm
  • elastin
  • tobacco smoke
  • vascular smooth muscle cell

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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