Nitroglycerin upregulates matrix metalloproteinase expression by human macrophages

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Immunology

Background:

• Nitroglycerin (NTG) is a common treatment for coronary artery disease, but its vascular effects are not fully understood.
• NTG's vasodilator activity does not consistently improve outcomes, suggesting potential pro-inflammatory actions.
• This study investigates NTG's impact on human monocyte-derived macrophages (MDMs).

Purpose of the Study:

• To investigate the effect of nitroglycerin (NTG) on matrix metalloproteinase (MMP) gene expression and activity.
• To determine if NTG influences the expression of tissue inhibitors of metalloproteinases (TIMPs).
• To assess the potential pro-inflammatory effects of NTG in human macrophages.

Main Methods:

• Human monocytes were differentiated into macrophages (MDMs).
• MDMs were treated with pharmacologically relevant doses of NTG or nitric oxide donors.
• MMP and TIMP activity, protein, and mRNA levels were quantified using zymography, ELISA, and RT-PCR.

Main Results:

• NTG significantly increased MMP-9 mRNA and activity in a dose-dependent manner.
• NTG also elevated mRNA levels for MMP-2 and MMP-7.
• NTG treatment decreased both mRNA and protein levels of TIMP-1, a key MMP inhibitor.

Conclusions:

• Pharmacologically relevant concentrations of NTG activate MMPs and repress TIMP expression in human macrophages.
• This NTG-induced imbalance in MMP/TIMP expression could lead to matrix degradation.
• Adverse effects on atherosclerotic plaque stability may result from NTG treatment.