Abnormal extracellular matrix mineralization is associated with some ofthe most prevalent and deadly diseases of western societies including atherosclerosis and arteriosclerosis. Understanding the molecular mechanisms by which abnormal matrix mineralization proceeds is an important first step toward better treatment for these diseases. Matrix Gla Protein (MGP) is an extracellular matrix protein that is a powerful suppressor of tissue mineralization. MGP knockout mice develop extreme aortic calcification, and MGP polymorphisms in humans are associated with increased risk of developing arterial calcification. Despite the important role of MPG in preventing vascular mineralization, the molecular mechanisms by which MGP expression is controlled and by which MGP functions are only partly understood. Our preliminary data and published results have shown that MGP controls Notch signaling, an important signaling pathway that synergizes with Bone Morphogenetic Proteins to control vascular biology. This observation has opened a door that may lead us to a better understanding of the role of MGP in vascular health. In this proposal, we will examine two specific aims. First, we believe we have identified a previously unknown negative feedback mechanism that we hypothesize serves an important role to control MGP expression and vascular extracellular matrix calcification. Second, we will continue to examine the molecular mechanism(s) by which MGP controls Notch signaling, an aspect of MGP function that we hypothesize is important for suppressing arterial matrix mineralization. Upon completion of these studies, we will arrive at a new understanding ofthe role of MGP in arterial health. As a Junior Investigator in the COBRE in Matrix Biology, I will work with my scientific mentor to complete the scientific aims and to develop a grant proposal for future R01 funding.

Public Health Relevance

Atherosclerosis and arteriosclerosis are of the most prevalent ailments of developed countries. Loss of elasticity in the walls ofthe arteries is due to extracellular matrix mineralization, or hardening ofthe arteries. Successful completion of these aims will lead to new understanding for the role of ECM in cardiovascular disease and improved treatment for arteriosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM109095-02
Application #
8898147
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Boise State University
Department
Type
DUNS #
072995848
City
Boise
State
ID
Country
United States
Zip Code
83725
Pinkaew, Decha; Chattopadhyay, Abhijnan; King, Matthew D et al. (2017) Fortilin binds IRE1? and prevents ER stress from signaling apoptotic cell death. Nat Commun 8:18
Doumas, Diana M; Esp, Susan; Flay, Brian et al. (2017) A Randomized Controlled Trial Testing the Efficacy of a Brief Online Alcohol Intervention for High School Seniors. J Stud Alcohol Drugs 78:706-715
Rohn, Troy T; Moore, Zachary D (2017) Nuclear Localization of Apolipoprotein E4: A New Trick for an Old Protein. Int J Neurol Neurother 4:
Thurston, John H; Hunter, Necia M; Wayment, Lacey J et al. (2017) Urea-derived graphitic carbon nitride (u-g-C3N4) films with highly enhanced antimicrobial and sporicidal activity. J Colloid Interface Sci 505:910-918
Styner, Maya; Pagnotti, Gabriel M; McGrath, Cody et al. (2017) Exercise Decreases Marrow Adipose Tissue Through ß-Oxidation in Obese Running Mice. J Bone Miner Res 32:1692-1702
Misra, Neha; Wines, Tyler F; Knopp, Colton L et al. (2017) Expression, immunogenicity and variation of iron-regulated surface protein A from bovine isolates of Staphylococcus aureus. FEMS Microbiol Lett 364:
Shrestha, Nisha; Bryant, Sheenah L; Thomas, Christopher et al. (2017) Stochastic sensing of Angiotensin II with lysenin channels. Sci Rep 7:2448
Miller, Robert A; Bond, Laura; Migas, Patrick N et al. (2017) CONTRASTING HABITAT ASSOCIATIONS OF SAGEBRUSH-STEPPE SONGBIRDS IN THE INTERMOUNTAIN WEST. West Birds 48:35-55
Love, Julia E; Day, Ryan J; Gause, Justin W et al. (2017) Nuclear uptake of an amino-terminal fragment of apolipoprotein E4 promotes cell death and localizes within microglia of the Alzheimer's disease brain. Int J Physiol Pathophysiol Pharmacol 9:40-57
Grassley, Jane S; Connor, Kelley C; Bond, Laura (2017) Game-based online antenatal breastfeeding education: A pilot. Appl Nurs Res 33:93-95

Showing the most recent 10 out of 53 publications