Pentraxin 3 Induces Vascular Endothelial Dysfunction Through a P-selectin/MMP-1 Pathway
Background—Pentraxin 3 (PTX3), the prototype of long pentraxins, has been described associated with endothelial dysfunction in different cardiovascular disorders. So far, no study has evaluated the possible direct effect of PTX3 on vascular function.
Methods and Results—Through in-vitro experiments of vascular reactivity and ultrastructural analyses, we demonstrate that PTX3 induces, per se, dysfunction and morphological changes of the endothelial layer through a P-selectin/metalloproteinase-1 (MMP1) pathway. The latter hampered the detachment of eNOS from Caveolin1, leading to an impairment of nitric oxide (NO) signaling. In vivo studies showed that the administration of PTX3 to wild-type mice induced endothelial dysfunction and increased blood pressure, an effect absent in P-selectin-deficient mice. In isolated endothelial cells (HUVEC), PTX3 significantly blunted NO production through the MMP1 pathway. Finally, using ELISA, we found that hypertensive patients (n=31) have higher plasma levels of PTX3 and its mediators P-Selectin and MMP1 than normotensive subjects (n=21).
Conclusions—Our data show for the first time a direct role of PTX3 on vascular function and blood pressure homeostasis, identifying the molecular mechanisms involved. The findings in humans suggest that PTX3, P-selectin and MMP-1 may be novel biomarkers that predict the onset of vascular dysfunction in hypertensive patients.
- Received December 11, 2014.
- Revision received February 4, 2015.
- Accepted February 13, 2015.