Low molecular weight fucan prevents transplant coronaropathy in rat cardiac allograft model.
BACKGROUND
Transplant arteriosclerosis is the main cause of long-term failure after cardiac transplantation. Vascular rejection is thought to be due to intimal proliferation occurring in response to arterial wall immune-mediated injury. A low molecular weight fucan (LMWF) compound, a sulfated polysaccharide, has been demonstrated to increase plasma levels of stromal cell-derived factor 1 (SDF-1) and consequently to mobilize bone marrow-derived vascular progenitor cells (BMVPC). The aim of this study was to evaluate the capacity of LMWF to prevent coronary intimal proliferation in a rat cardiac allograft model.


METHODS
Heterotopic abdominal cardiac graftings were performed in Brown Norway (BN) and Lewis (LEW) rats. Animals were divided into 4 groups of 10 rats. Two groups were treated intramuscularly with LMWF (5 mg/kg/day) (one BN to BN isograft group, and one BN to LEW allograft group); and two control groups were LMWF-untreated (one BN to BN isograft group and one BN to LEW allograft group). All animals were treated by cyclosporin (15 mg/kg/day) sub-cutaneously and sacrificed at day 30. The cardiac grafts were assessed by morphometry of structural parameters and by histological and immunohistochemical analyses.


RESULTS
All cardiac isografts were devoid of any coronary and parenchymal lesions. In contrast, the majority of untreated allografts developed coronary intimal proliferation in close association with intimal and adventitial inflammatory CD68(+) cell infiltration. Further, the parenchyma exhibited large areas of actin(+) cells (myofibroblasts) of recipient origin colocalized with the CD68(+) infiltrating cells. Interestingly, all LMWF-treated allografts were well protected against coronary and parenchymal lesions and the coronary arteries exhibited an intimal monolayer of flat cells, which however were CD34 negative.


CONCLUSIONS
treatment with LMWF appeared very effective in this rat cardiac allograft model to prevent arterial and parenchymal lesions occurring in response to alloimmune injury. However this protective effect does not appear to depend on mobilization of bone marrow-derived cells.
Alkhatib
Bassam
B
Cardiac and Vascular Surgery Departments, Rouen University Hospital, France.
Freguin-Bouilland
Caroline
C
Lallemand
Françoise
F
Henry
Jean Paul
JP
Litzler
Pierre-Yves
PY
Marie
Jean Paul
JP
Richard
Vincent
V
Thuillez
Christian
C
Plissonnier
Didier
D
D000818:Animals; D049109:Cell Proliferation; D003324:Coronary Artery Disease / Q000473:pathology / Q000517:prevention & control*; D005643:Fucose / Q000502:physiology; D006131:Growth Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology; D016027:Heart Transplantation / Q000009:adverse effects; D008297:Male; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000473:pathology; D011134:Polysaccharides / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013463:Sulfuric Acid Esters / Q000494:pharmacology; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000166:cytology
D006131:Growth Inhibitors; D011134:Polysaccharides; D013463:Sulfuric Acid Esters; D005643:Fucose; C007789:fucoidan