Endothelial nitric oxide synthase deficiency enhanced carotid artery ligation-induced remodeling by promoting vascular inflammation

Le Ning Zhang, Valdeci Da Cunha, Baby Martin-McNulty, Dennis W Wilson, Mark E. Sullivan, Ronald Vergona, John C Rutledge, Yi Xin Wang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Nitric oxide (NO) plays an important role in vascular protection. It has been reported that endothelial NO synthase (eNOS) deficiency exacerbated carotid artery ligation (CAL)-induced vascular remodeling, which, however, did not elucidate the role of inflammation. Overexpression of eNOS inhibited vascular inflammation and remodeling in a CAL model. However, there is no study that tested the hypothesis that eNOS deficiency can enhance the inflammatory response that plays a critical role in exacerbation of CAL-induced vascular remodeling. Thus, the present study used both eNOS knockout (eNOS-KO) mice and pharmacological blockade of nitric oxide synthase (NOS) to examine the temporal relationship between the inflammatory process and vascular remodeling by CAL and how elimination of NO production affects this. The left common carotid artery was ligated in eNOS-KO, or wild type (WT) mice treated with or without an NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). In WT mice, CAL induced vascular inflammation, characterized by neutrophil and macrophage infiltration into the vessel wall at 1 week. Although the inflammation diminished at 4 weeks, the ligated carotid artery developed prominent vascular remodeling, manifested by smooth muscle cell rich neointimal formation, medial thickening, and adventitial proliferation with reduced luminal diameter. CAL also increased the expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1).VCAM-1 peaked at 1 week, and then slightly declined 4 weeks after CAL, while MCP-1 continued to increase. In eNOS-KO mice, the above changes were exacerbated. Treatment with L-NAME resulted in similar changes as in eNOS-KO mice. Thus, in complement to the previous finding that eNOS overexpression inhibited CAL-induced vascular remodeling, the present study further demonstrated that the absence of eNOS exacerbated vascular remodeling by promoting MCP-1 and VCAM-1 mediated vascular inflammation. These data provided further in vivo evidence supporting the hypothesis that vasculo-protective effects of eNOS are mediated, at least in part, by inhibition of vascular inflammation and smooth muscle cell migration and proliferation induced by vascular injury and blood flow cessation.

Original languageEnglish (US)
Pages (from-to)100-114
Number of pages15
JournalJournal of Applied Research
Volume6
Issue number2
StatePublished - 2006

Fingerprint

Nitric Oxide Synthase Type III
Carotid Arteries
Nitric Oxide Synthase
Ligation
Inflammation
Vascular Cell Adhesion Molecule-1
Chemokine CCL2
NG-Nitroarginine Methyl Ester
Blood Vessels
Smooth Muscle Myocytes
Nitric Oxide
Vascular Remodeling
Adventitia
Neutrophil Infiltration
Vascular System Injuries
Common Carotid Artery
Vascular Smooth Muscle
Knockout Mice
Cell Movement
Macrophages

Keywords

  • Atherosclerosis
  • eNOS knockout mice
  • Macrophage
  • Monocyte chemoattractant protein-1
  • Nitric oxide
  • Remodeling
  • Restenosis
  • Smooth muscle cell
  • Vascular cell adhesion molecule-1
  • Vessel inflammation

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology

Cite this

Zhang, L. N., Da Cunha, V., Martin-McNulty, B., Wilson, D. W., Sullivan, M. E., Vergona, R., ... Wang, Y. X. (2006). Endothelial nitric oxide synthase deficiency enhanced carotid artery ligation-induced remodeling by promoting vascular inflammation. Journal of Applied Research, 6(2), 100-114.

Endothelial nitric oxide synthase deficiency enhanced carotid artery ligation-induced remodeling by promoting vascular inflammation. / Zhang, Le Ning; Da Cunha, Valdeci; Martin-McNulty, Baby; Wilson, Dennis W; Sullivan, Mark E.; Vergona, Ronald; Rutledge, John C; Wang, Yi Xin.

In: Journal of Applied Research, Vol. 6, No. 2, 2006, p. 100-114.

Research output: Contribution to journalArticle

Zhang, Le Ning ; Da Cunha, Valdeci ; Martin-McNulty, Baby ; Wilson, Dennis W ; Sullivan, Mark E. ; Vergona, Ronald ; Rutledge, John C ; Wang, Yi Xin. / Endothelial nitric oxide synthase deficiency enhanced carotid artery ligation-induced remodeling by promoting vascular inflammation. In: Journal of Applied Research. 2006 ; Vol. 6, No. 2. pp. 100-114.
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