Alprostadil liposome microsphere preparation stabilizes vascular plaques and inhibits intra-plaque inflammation

Background Vulnerable plaques play an important role in the onset of sudden cardiac events and strokes. How to stabilize vulnerable plaques is still a challenge to medical science. Alprostadil is a biologically active substance with strong activity on vessel. Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation （ALMP） on vulnerable plaques in the brachiocephalic artery of apolipoprotein E （Apo E） knockout mice. Methods Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age. At week 17, they were divided randomly into groups for treatment with a high dose （3.6 μg, kg-1. d-1） or low dose （1.8 μg. kg-1 . d-1） of an ALMP, or 0.2 ml/d normal saline （control group）, The drug was administered using a micro-capsule pump. Twenty weeks after drug administration, pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed, and levels of anti-mouse monocyte/macrophage monoclonal antibody （MOMA-2） and superoxide anions in the plaques were detected using immunofluorescence. The soluble intercellular adhesion molecule-1 （ICAM-1） expression was measured by ELISA, and the expression of matrix metalloproteinase-9 （MMP-9） and CD40 mRNA was measured using RT-PCR. Thrombospindin-1 （TSP-1） expression was detected using Western blotting. Results Compared with the control group, ALMP treatment significantly reduced the plaque area in the brachiocephalic artery （P 〈0.01）, significantly lowered the contents of the lipid core （P 〈0.01 ）, significantly reduced the number of ruptured fibrous caps （P 〈0.05）, and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage （P 〈0.05）. ALMP treatment significantly reduced the expression of MOMA-2, superoxide anion, MMP-9, ICAM-1 and CD40 in the plaques （P 〈0.01）, decreased plasma ICAM-1 expression （P 〈0.01 ）, and increased the expression of TSP-1. Conclusions Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.