2011 Fiscal Year Final Research Report
Elucidation of the arteriosclerosis control mechanism of soluble Flt-1 in the renal insufficiency
| Project/Area Number |
22790722
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Nara Medical University |
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Principal Investigator |
TAKEDA Yukiji 奈良県立医科大学, 医学部, 助教 (60398443)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 分子心臓病態学 |
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| Research Abstract |
Placental growth factor(PlGF), a family of VEGF, plays important roles in the development of atherosclerosis, which is antagonized by sFlt-1.In our study, plasma sFlt-1 level was positively correlated with eGFR in the 329 patients underwent cardiac catheterization(after 20-Unit heparin administration). The PlGF/sFlt-1 ratio was significantly correlated with multi-vessel coronary artery disease.
Heparin is reported to affect on plasma sFlt-1 level, we have to consider the effect of heparin during the cardiac catheterization. We hypothesized that the heparin-induced increment of plasma sFlt-1 level would indicate the total circulating sFlt-1 and systemic release from endothelial cells. Plasma sFlt-1 levels increased in 251 CKD patients after heparin injection(0.4IU/Kg) and that the level was positively correlated with eGFR, though the effect is opposite in baseline circulating sFlt-1 level. Mice study also revealed that sFlt-1 mRNA expression in organs examined(kidney, lung) was suppressed by about 50% in 5/6 nephrectomized mice, indicating total amount of sFlt-1 was decreased in CKD.
Analysis of 343 CKD patients revealed that patients with higher PlGF/sFlt-1 ratio after heparin injection had significantly higher risk of acute cardiac death plus total cardiovascular event compared to lower ratio.
Atherosclerotic plaque area and macrophage infiltration into the plaque were significantly increased in 5/6 nephrectomized ApoE-deficient mice ; a model of atherosclerosis in renal failure. Replacement therapy with recombinant sFlt-1 significantly reduced atherosclerotic plaque formation.
PlGF/sFlt-1 has an important role in atherosclerotic process of CKD patients.
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