Micro-CT > Background Section
Renal Angiography: We are regularly obtaining high-resolution 100ƒÝm isotropic resolution angiography data sets for small animal cancer models employing the intravascular contrast agent Gd-DTPA-albumin. Figure 1 depicts a 3D example of the neovasculature associated with a LLC tumor model. This technique could potentially be applicable to longitudinally and quantitatively assess treatments and disease models (e.g. hypertension and atherosclerosis) designed to alter the kidney vasculature.
(Developmental Studies for Angiography)
To assess the utility of MR angiography to detect abnormal renal vascular architecture we will compare renal angiograms of control mice to those collected in eNOS/ApoE and/or prostacylin (PGI2) synthesis mice, which are well-characterized models of atherosclerosis (1, 2). The detection of vascular abnormalities will be validated using vascular casting techniques as well as histological examinations.
Publications for Micro-CT (2)
Yokoyama C, Yabuki T, Shimonishi M, Wada M, Hatae T, Ohkawara S, Takeda J, Kinoshita T, Okabe M, Tanabe T. Prostacyclin-deficient mice develop ischemic renal disorders, including
nephrosclerosis and renal infarction. Circulation (2002) 106:2397-403
View abstract View in PubMed
BACKGROUND: Prostacyclin (PGI2) is a short-lived endogenous inhibitor of platelet aggregation and a potent vasodilator and regulator of the growth of vascular smooth muscle cells. To study the role of PGI2 in the vascular system in vivo, PGI2-deficient (PGID) mice were established by genetic disruption of the PGI2 synthase gene. METHODS AND RESULTS: PGI2 synthase-null mice were generated by replacing the exons of PGI2 synthase gene that encodes for the catalytic site of the enzyme with a neomycin resistance gene. In these mice, PGI2 levels in the plasma, kidneys, and lungs were reduced, whereas thromboxane and prostaglandin E2 levels became elevated. Blood pressure and the amounts of urea nitrogen and creatinine in plasma of the PGID mice were significantly higher than those of wild-type mice (P<0.05). They developed progressive morphological abnormalities in the kidneys, accompanied by atrophy, surface irregularity, fibrosis, cyst, arterial sclerosis, and hypertrophy of vessel walls. Thickening of the thoracic aortic media and adventitia were observed in aged PGID mice. Importantly, these phenotypes have not been reported in PGI2 receptor-deficient mice. CONCLUSIONS: PGI2 deficiency resulted in the development of vascular disorders with the thickening of vascular walls and interstitial fibrosis, especially in mouse kidneys. The findings demonstrated in vivo that PGI2 is important in the homeostasis of blood vessels. Our established PGID mice are useful for studies on the initiation and development of vascular diseases, such as ischemic renal disorders with arterial sclerosis and infarction, and also for studies on the novel signaling pathway of PGI2.
Knowles JW, Reddick RL, Jennette JC, Shesely EG, Smithies O, Maeda N. Enhanced atherosclerosis and kidney dysfunction in eNOS(-/-)Apoe(-/-) mice
are ameliorated by enalapril treatment. J Clin Invest (2000) 105:451-8
View abstract View in PubMed
Hypertension and atherosclerosis are each important causes of morbidity and mortality in the developed world. We have investigated the interaction between these conditions by breeding mice that are atherosclerotic due to lack of apolipoprotein (apo) E with mice that are hypertensive due to lack of endothelial nitric oxide synthase (eNOS). The doubly deficient mice (nnee) have higher blood pressure (BP) and increased atherosclerotic lesion size but no change in plasma lipoprotein profiles compared with normotensive but atherosclerotic (NNee) mice. The nnee mice also develop kidney damage, evidenced by increased plasma creatinine, decreased kidney weight/body weight ratio, and glomerular lipid deposition and calcification. Enalapril treatment abolishes the deleterious effects of eNOS deficiency on BP, atherosclerosis, and kidney dysfunction in nnee mice. In striking contrast, a genetic lack of inducible NOS, which does not affect BP, has no effect on the development of atherosclerotic lesions in Apoe(-/-) mice. We also observed a positive relationship between BP and size of atherosclerotic lesions These results suggest that the atherogenic effects of eNOS deficiency can be partially explained by an increase in BP and reemphasize the importance of controlling hypertension in preventing atherosclerosis.
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Last updated on 2008-01-28 Moderated by Takamune Takahashi