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Alprostadil liposome microsphere preparation stabilizes vascular plaques and inhibits intra-plaque inflammation.
- Source :
-
Chinese medical journal [Chin Med J (Engl)] 2012 Dec; Vol. 125 (24), pp. 4380-5. - Publication Year :
- 2012
-
Abstract
- 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.<br />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.<br />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.<br />Conclusions: Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.
- Subjects :
- Animals
Enzyme-Linked Immunosorbent Assay
Inflammation drug therapy
Inflammation metabolism
Inflammation pathology
Intercellular Adhesion Molecule-1 metabolism
Male
Mice
Mice, Knockout
Microscopy, Fluorescence
Plaque, Atherosclerotic metabolism
Polymerase Chain Reaction
Alprostadil chemistry
Alprostadil therapeutic use
Liposomes chemistry
Microspheres
Plaque, Atherosclerotic drug therapy
Plaque, Atherosclerotic pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2542-5641
- Volume :
- 125
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Chinese medical journal
- Publication Type :
- Academic Journal
- Accession number :
- 23253706