Vascular remodeling and mobilization of bone marrow-derived cells in cuff-induced vascular injury in LDL receptor knockout muce
- Author:
- No author available
- Journal Title:
- CHINESE MEDICAL JOURNAL
- Issue:
- 3
- DOI:
- No doi available
- Key Word:
- vascular remodeling;macrophage;smooth muscle cell;endothelial cell;bone marrow
Abstract： Background Vascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis,postangioplasty restenosis and transplant arteriopathy.Recently,pathologic change and the role of bone marrow derived cells were wildly studied in atherosclerosis and restenosis.But the manner of lesion formation in neointima and cell recruitment in vascular remodeling lesion in the present of hypercholesterolemia is not Vet fully understood. Methods Double-transgenic mice knockout of LDL receptor gene (LDL-/-) and expressing ubiquitously green fluorescent protein (GFP) were obtained by cross-breeding LDL-/-mice with the GFP-expressing transgenic mice. LDL-/- mice (22-24 weeks of age) fed high fat diet containing 1.25% (w/w) cholesterol were subjected to 9Gy irradiation and received bone marrow (BM) cells from the double-transgenic mice.Four weeks later,a nonconstrictive cuff was Dlaced around the right femoral artery.After another 2 weeks,both right and left femoral arteries were harvested and subjected to histochemical analysis.Apoptosis was analyzed in situ using TUNEL assay.Resuits Two weeks after cuff placement,atherosclerotic lesions developed in the intima consisting of a massive accumulation of foam cells, The tissue stained with anti-α smooth muscle actin (SMA) antibody,showed a number of SMA-positive cells in the intimal lesion area.They were also positive for GFP,indicating that BM-derived cells can differentiate to SMCs in the intima in cuff-induced vascular remodeling lesions.Numerous small vessels in the adventitia as well as the endothelial lining of the intima were positive both for CD31 and GFP.The intima and media showed a larae number of TUNEL-positive signals after 2 weeks cuff injury,indicating the presence of apoptosis in vascular remodelina.Conclusions Atherosclerotic lesions in mice can be developed in the intima after 2 weeks of cuff-induced vascular inJury under the hypercholesterolemic conditions.Our data also clearly indicate that bone marrow-derived cells differentiated to smooth muscles and endothelial cells in the formation of these lesions in the presence of hypercholesterolemia.
- [1]John H. Ip,Valentin Fuster,Lina Badimon,etc.Syndromes of accelerated atherosclerosis: Role of vascular injury and smooth muscle cell proliferation[J].1990,15(7).
- [2]Vilde F,Guerot C,Tedgui A,etc.Time courses of apoptosis and cell proliferation and their relationship to arterial remodeling and restenosis after angioplasty in an atherosclerotic rabbit model.[J].2002,39(10).
- [3]Ross R.Atherosclerosis--an inflammatory disease.[J].1999,340(2).
- [4]T, Murayama,M, Yokode,H, Kataoka,etc.Intraperitoneal administration of anti-c-fms monoclonal antibody prevents initial events of atherogenesis but does not reduce the size of advanced lesions in apolipoprotein E-deficient mice.[J].1999,99.
- [5]Yang, Xu,Hidenori, Arai,Xin, Zhuge,etc.Role of bone marrow-derived progenitor cells in cuff-induced vascular injury in mice.[J].2004,24(3).
- [6]Nicoletti A,Hansson GK,Kaveri S,etc.Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice.[J].1998,102(5).
- [7]Han CI,Campbell GR,Campbell JH.Circulating bone marrow cells can contribute to neointimal formation.[J].2001,38(2).
- [8]Kita T,Sano H,Kataoka H,etc.Functional blockade of platelet-derived growth factor receptor-beta but not of receptor-alpha prevents vascular smooth muscle cell accumulation in fibrous cap lesions in apolipoprotein E-deficient mice.[J].2001,103(24).
- [9]Shimizu K,Rabkin E,Aikawa M,etc.Host bone-marrow cells are a source of donor intimal smooth- muscle-like cells in murine aortic transplant arteriopathy.[J].2001,7(6).
- [10]Hirata Y,Makuuchi M,Okada S,etc.Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis.[J].2002,8(4).
- [11]Sata M,Nagai R,Makuuchi M,etc.Circulating smooth muscle progenitor cells contribute to atherosclerosis.[J].2001,7(4).
- [12]Achmad, Rudijanto.The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis.[J].1900,39(2).
- [13]Cui TX,Takeda Matsubara Y,Liu HW,etc.Effect of estrogen and AT1 receptor blocker on neointima formation.[J].2002,40(4).
- [14]J M, Isner,M, Kearney,S, Bortman,etc.Apoptosis in human atherosclerosis and restenosis.[J].1995,91.
- [15]M G, Davies,P O, Hagen.Pathophysiology of vein graft failure: a review.[J].1995,9(1).