CORE B: Physiology and Animal Resource Core SUMMARY The Physiology and Animal Resource Core B is a critical for the proposed research as it assists investigators with the equipment and expertise to facilitate in vivo and ex vivo physiological experiments in anesthetized and conscious rodents as well as to provide animals for the individual projects of the PPG. Core B will accomplish these goals by executing the following specific aims:
Specific Aim 1 : To assist investigators in Projects 1 and 3 with: a)- chronic measurements of arterial pressure using telemetry probes; b)- osmotic mini-pump implantation for drug delivery; c)- functional determinations of cardiac dynamics using conductance catheters; d)- longitudinal analysis of cardiac structure and function by transthoracic echocardiography; e)-comprehensive analysis of blood flow (including coronary and renal arteries), organ perfusion using contrast imaging functionality on the Vevo LAZR and microbubble perfusion;, f)- use of a Langendorff apparatus for assessment of cardiac performance and metabolism; g)-cardiac microdialysis for biochemical analysis of interstitial fluid (ISF).
Specific Aim 2 : To provide animals for the individual projects of the PPG by: a) maintaining a breeder colony of cardiomyocyte-specific, doxycyline-inducible GPR30 knockout mice (GPR30KO) for the purposes of Project 3; b) overseeing the procurement of rats and mice from commercial vendors (Wistar-Kyoto and Spontaneously Hypertensive Rats, - Project 1; and C57Bl/6 mice - Project 3) and Transgenic Rat Facility of the Hypertension Vascular Research Center, Wake Forest University [rats harboring the complete genomic human angiotensinogen (AGT) gene [(hAGT)L1623 TG rats] and mRen2.Lewis rats] to meet scientific objectives in Projects 1 and 3; c) establishing colonies of transgenic rats expressing cardiac human chymase as well as double transgenic rats expressing human angiotensinogen and chymase for the scientific purposes of all Projects.

Public Health Relevance

CORE B: Physiology and Animal Resource Core NARRATIVE/RELEVANCE The overall goal of the Physiology Core is to assist investigators primarily in Projects 1 and 3 with the equipment and expertise to facilitate in vivo and ex vivo physiological experiments in anesthetized and conscious rodents as well as to provide animals for the individual projects of the PPG.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL051952-21A1
Application #
8794001
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
2020-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
21
Fiscal Year
2015
Total Cost
$436,165
Indirect Cost
$150,865
Name
Wake Forest University Health Sciences
Department
Type
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
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Ahmad, Sarfaraz; Sun, Xuming; Lin, Marina et al. (2018) Blunting of estrogen modulation of cardiac cellular chymase/RAS activity and function in SHR. J Cell Physiol 233:3330-3342
Li, Tiankai; Zhang, Xiaowei; Cheng, Heng-Jie et al. (2018) Critical role of the chymase/angiotensin-(1-12) axis in modulating cardiomyocyte contractility. Int J Cardiol 264:137-144
Dell'Italia, Louis J; Collawn, James F; Ferrario, Carlos M (2018) Multifunctional Role of Chymase in Acute and Chronic Tissue Injury and Remodeling. Circ Res 122:319-336
Ola, Mohammad Shamsul; Alhomida, Abdullah S; Ferrario, Carlos M et al. (2017) Role of Tissue Renin-angiotensin System and the Chymase/angiotensin-( 1-12) Axis in the Pathogenesis of Diabetic Retinopathy. Curr Med Chem 24:3104-3114
Ferrario, Carlos M; Mullick, Adam E (2017) Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease. Pharmacol Res 125:57-71
Chappell, Mark C; Al Zayadneh, Ebaa M (2017) Angiotensin-(1-7) and the Regulation of Anti-Fibrotic Signaling Pathways. J Cell Signal 2:
Alencar, Allan K; da Silva, Jaqueline S; Lin, Marina et al. (2017) Effect of Age, Estrogen Status, and Late-Life GPER Activation on Cardiac Structure and Function in the Fischer344×Brown Norway Female Rat. J Gerontol A Biol Sci Med Sci 72:152-162
Guichard, Jason L; Rogowski, Michael; Agnetti, Giulio et al. (2017) Desmin loss and mitochondrial damage precede left ventricular systolic failure in volume overload heart failure. Am J Physiol Heart Circ Physiol 313:H32-H45

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