CC, ERGUL The projects in this Program Project Grant application focus on two key damage associated molecular patterns (DAMPs), high mobility group box 1 (HMGB1) and mitochondrial (mt) DNA, activating the innate immune response via their respective pattern recognition receptors (PPRs) TLR4 and TLR9 resulting in stimulation of a number of cytokines in experimental animal models of hypertension. The Bioinflammation Core (Core C) is structured to serve all three projects with centralized measurements of DAMPs, PRRs, immune cells and downstream cytokines to facilitate the success of the individual projects and achieve the overall goals of this Program Project. The secondary goal is to provide necessary services to enhance the synergy among projects. Core C will be directed by Dr. Ergul and supported by Dr. Babak Baban. Both investigators have a long- standing record of analyzing experimental and clinical specimens with a highly qualified staff. A centralized Core is essential to the success of each project and the Program Project as a whole and offers the following benefits: 1. The coordination of sample preparation within the Bioinflammation Core C will benefit all Projects as Core C will optimize sample recovery and increase efficiency and rigor by allowing analysis of more samples in one run while providing blinded analyses of the samples. 2. Common approach (in many cases identical methods and reagents) to measure the same markers across the projects will provide synergy, quality control and consistency among the projects. 3. The measurement of primary and secondary DAMPs/PRRS in all Projects will cross cultivate the Projects and allow the development of new venues of investigation that otherwise would not have been possible with regular R01 applications. 4. Higher numbers of measurements will be completed at a relatively lower cost with highly skilled research personnel. 5. A close interaction with the Animal Models Core (Core B) will ensure proper collection and storage of specimens and increase reproducibility.

Public Health Relevance

CC, ERGUL Uncontrolled hypertension increases the risk of chronic kidney disease, stroke, heart attack, heart failure and peripheral artery disease and in ~85% of cases, the cause of hypertension remains unknown. The proposed project (Core C) will provide centralized measurements and provide quality control for 3 projects in the program project addressing novel immune mechanisms that may contribute to the development and consequences of hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL134604-01
Application #
9209301
Study Section
Special Emphasis Panel (HLBP (JH))
Program Officer
Maric-Bilkan, Christine
Project Start
Project End
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
1
Fiscal Year
2017
Total Cost
$291,943
Indirect Cost
$99,875
Name
Augusta University
Department
Type
Domestic Higher Education
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912
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McCarthy, Cameron G; Wenceslau, Camilla F (2018) Adopting an Orphan: How Could GRP35 Contribute to Angiotensin II-Dependent Hypertension? Am J Hypertens 31:973-975
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Komic, Amel; Martinez-Quinones, Patricia; McCarthy, Cameron G et al. (2018) Increase in soluble protein oligomers triggers the innate immune system promoting inflammation and vascular dysfunction in the pathogenesis of sepsis. Clin Sci (Lond) 132:1433-1438
Gonçalves, Tiago Tomazini; Lazaro, Carolina M; De Mateo, Fernanda G et al. (2018) Effects of glucosyl-hesperidin and physical training on body weight, plasma lipids, oxidative status and vascular reactivity of rats fed with high-fat diet. Diabetes Metab Syndr Obes 11:321-332
Wynne, Brandi M; McCarthy, Cameron G; Szasz, Theodora et al. (2018) Protein kinase C? deletion causes hypotension and decreased vascular contractility. J Hypertens 36:510-519

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