Vascular calcification is highly correlated with cardiovascular disease (CVD) mortality, especially in end stage renal disease (ESRD) and diabetic patients. In addition to the devastating effects of inappropriate biomineralization seen in cardiac valvulopathies, calciphylaxis and idiopathic infantile arterial calcification, vascular calcification is now recognized as a marker of atherosclerotic plaque burden as well as a major contributor to loss of arterial compliance and increased pulse pressure seen with age, diabetes and renal insufficiency. Whether or not vascular calcification can cause or exacerbate atherosclerosis is not known, and will be addressed in this proposal. Furthermore, arterial wall cells appear to play a particularly important role in mediating vascular calcification, especially in situations where osteochondral tissue is observed, such as in atherosclerosis and medial calcification associated with ESRD. This proposal seeks to identify the origins of the cells participating in osteochondral tissue formation, and mechanisms controlling their differentiation. These studies will aid in the development of novel therapeutic strategies to prevent and potentially reverse vascular calcification, an urgent need in the ESRD population. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL081785-04
Application #
7471401
Study Section
Atherosclerosis and Inflammation of the Cardiovascular System Study Section (AICS)
Program Officer
Srinivas, Pothur R
Project Start
2005-09-01
Project End
2010-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
4
Fiscal Year
2008
Total Cost
$369,790
Indirect Cost
Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Yamada, Shunsuke; Leaf, Elizabeth M; Chia, Jia Jun et al. (2018) PiT-2, a type III sodium-dependent phosphate transporter, protects against vascular calcification in mice with chronic kidney disease fed a high-phosphate diet. Kidney Int 94:716-727
Yamada, Shunsuke; Wallingford, Mary C; Borgeia, Suhaib et al. (2018) Loss of PiT-2 results in abnormal bone development and decreased bone mineral density and length in mice. Biochem Biophys Res Commun 495:553-559
Scatena, Marta; Jackson, Melissa F; Speer, Mei Y et al. (2018) Increased Calcific Aortic Valve Disease in response to a diabetogenic, procalcific diet in the LDLr-/-ApoB100/100 mouse model. Cardiovasc Pathol 34:28-37
Jackson, Melissa F; Scatena, Marta; Giachelli, Cecilia M (2017) Osteoclast precursors do not express CD68: results from CD68 promoter-driven RANK transgenic mice. FEBS Lett 591:728-736
Yamada, Shunsuke; Giachelli, Cecilia M (2017) Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho. Bone 100:87-93
Giachelli, Cecilia M; Speer, Mei Y (2017) Noncanonical Wnts at the Cusp of Fibrocalcific Signaling Processes in Human Calcific Aortic Valve Disease. Arterioscler Thromb Vasc Biol 37:387-388
Wallingford, Mary Catherine; Chia, Jia Jun; Leaf, Elizabeth M et al. (2017) SLC20A2 Deficiency in Mice Leads to Elevated Phosphate Levels in Cerbrospinal Fluid and Glymphatic Pathway-Associated Arteriolar Calcification, and Recapitulates Human Idiopathic Basal Ganglia Calcification. Brain Pathol 27:64-76
Paloian, Neil J; Leaf, Elizabeth M; Giachelli, Cecilia M (2016) Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification. Kidney Int 89:1027-1036
Wallingford, Mary C; Gammill, Hilary S; Giachelli, Cecilia M (2016) Slc20a2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and laminin?1 expressing cells. Reprod Biol 16:13-26
Lin, Mu-En; Chen, Theodore; Leaf, Elizabeth M et al. (2015) Runx2 Expression in Smooth Muscle Cells Is Required for Arterial Medial Calcification in Mice. Am J Pathol 185:1958-69

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