Related Experiment Video
Updated: Aug 11, 2026
A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis
Published on: May 14, 2013
Neutrophil antimicrobial peptide alpha-defensin causes endothelial dysfunction in porcine coronary arteries
Panagiotis Kougias1, Hong Chai, Peter H Lin
1Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Insights
Alpha-defensin, a neutrophil antimicrobial peptide, impairs blood vessel function by increasing superoxide production and reducing nitric oxide synthase. This finding suggests targeting alpha-defensin may offer new strategies for preventing vascular diseases.
Area of Science:
- Vascular Biology
- Inflammation and Immunity
Background:
- Defensins are antimicrobial peptides released by neutrophils.
- Inflammation, involving neutrophil infiltration and defensin release, is implicated in atherosclerosis and vascular diseases.
Purpose of the Study:
- To investigate the effect of alpha-defensin on endothelial dysfunction in porcine coronary arteries.
- To explore the molecular mechanisms underlying alpha-defensin-induced endothelial dysfunction.
Main Methods:
- Porcine coronary artery rings were treated with human recombinant alpha-defensin.
- Vasomotor reactivity was assessed using a myograph system.
- Superoxide anion levels and endothelial nitric oxide synthase (eNOS) mRNA and protein expression were quantified.
Main Results:
- Alpha-defensin significantly reduced endothelium-dependent relaxation by 40% without affecting endothelium-independent relaxation.
- Superoxide anion levels increased by 80% in treated vessels.
- eNOS mRNA and protein levels were significantly decreased by 27% and substantially reduced, respectively.
Conclusions:
- Alpha-defensin impairs endothelium-dependent vasorelaxation in coronary arteries.
- This effect is linked to increased superoxide production and decreased eNOS expression.
- Targeting alpha-defensin may represent a novel therapeutic strategy for vascular diseases.
Background:
Defensins are cysteine-rich cationic polypeptides released from neutrophils that exhibit powerful antimicrobial activities. Because inflammation, including neutrophil infiltration and release of defensins, may play an important role in atherosclerosis and other vascular diseases, we determined whether alpha-defensin could cause endothelial dysfunction, a major initial event of atherosclerosis, in porcine coronary arteries.
Methods:
Porcine coronary arteries were sliced into 5-mm rings and treated with different concentrations of human recombinant alpha-defensin for 24 hours. Vasomotor reactivity was studied by using a myograph system. Levels of superoxide anion were detected by the lucigenin-enhanced chemiluminescence method. Endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA) and protein levels were determined by real-time polymerase chain reaction and immunohistochemistry analysis, respectively.
Results:
Endothelium-dependent relaxation in response to bradykinin was significantly reduced by 40% for the rings treated with 1500 nM of alpha-defensin compared with controls (P< .05). Vessel contractility in response to the thromboxane A2 analogue U46619 and endothelium-independent relaxation in response to sodium nitroprusside were not affected with defensin treatment. In addition, the superoxide anion level at the endothelial layer of porcine coronary artery rings was significantly increased by 80% in the defensin-treated (1500 nM) vessels compared with controls (P< .05). Furthermore, the eNOS mRNA levels in endothelial cells isolated from the cultured rings treated with defensin (1500 nM) were significantly decreased by 27% compared with controls (P< .05). Immunoreactivity of eNOS in the defensin-treated vessel rings was also substantially reduced.
Conclusions:
Defensin reduces the endothelium-dependent vasorelaxation. This effect is associated with increased superoxide radical production and decreased eNOS expression in porcine coronary arteries.
Clinical Relevance:
Inflammation is an important mechanism of atherosclerosis and other vascular diseases. The roles and interactions of biomediators released from inflammatory cells are not fully understood, however. This study provides new information about effects and potential molecular mechanisms of a major neutrophil releasing factor, alpha-defensin, on endothelial dysfunction of porcine coronary arteries. Thus, targeting alpha-defensin and its associated molecular mechanisms may become a new strategy to prevent vascular diseases.
