The Animal Physiology, Surgery and Imaging Core (Core C) will be used by all the Projects of this PPG to support the global hypothesis that impairment of the autophagic pathway occurring with aging and metabolic syndrome (MetS) is involved in the development, progression, and clinical outcome of cardiovascular disease. More specifically it is proposed that altered autophagy occurring in the aged or individuals with MetS contributes to inflammation, increases the extent and susceptibility of the heart to ischemic injury, and exacerbates adverse cardiac remodeling associated with myocardial infarction. It is further proposed that pharmacologic modulation of autophagy is a viable strategy to decrease the negative cardiac consequences associated with ischemic injury in aged individuals or those with MetS. A key focus of this proposal is the employment of in-vivo animal models that reproduce many of the features associated with aging and metabolic syndrome. In this regard it is essential that the animal models to be used are well characterized with respect to metabolic state and cardiovascular function, and are consistently uniform from study to study. Additionally, as tissue (blood, heart, spleen) from conditioned animals will be used across multiple projects as well as provided to the proteomics core, it will be critical! that a tracking system be in place to allow correspondence of ex-vivo biochemical and molecular data with the phenotype of the animal of origin. This Core will provide project support in 5 defined areas. 1) Working in conjunction with the institutional vivarium personnel, the core will maintain, provide, characterize, and coordinate use of conditioned animals;2) Provide surgical support (acute and chronic Ml induction);3) Provide invasive and non-invasive standardized assessments of cardiac function (cardiac catheterization, cardiac ultrasound);4) Provide standardized assessments of metabolic status (lipids, glucose, insulin sensitivity);and 5) Support imaging assessments of autophagy and LV remodeling (microscopy, IVIS). Collectively, the personnel in the core bring together unique knowledge and technical expertise in the design and conduct of clinically translational in-vivo animal studies from rodent to large animal in the area of metabolic disease, myocardial infarction, LV remodeling, and cardioprotection, A major strength of this program is the utilization of a number of well characterized animal species to investigate the overall hypothesis, recognizing that each has its strengths and limitations with regard to scientific and translation relevance, as well as practical considerations such as cost and resource requirement. By taking the approach of conducing initial hypothesis testing/ validating studies in conditioned and genetic mouse and rat models, and advancing to confirmation studies in swine, we believe we can generate robust and clinically relevant information which can support the development of a novel cardioprotective strategy by the Projects.

Public Health Relevance

The Animal Physiology, Surgery and Imaging Core (Core C) will be used by all ofthe Projects of this PPG. Core C will offer integrated services for maintaining and characterizing the metabolic status of the animals, performing the surgeries and measuring cardiac function under acute and chronic myocardial infarction conditions, and supporting the imaging assessments of autophagy and left ventricular remodeling. Core C will maintain the equipment and provide the staff and services necessary for the Project leaders and other PPG personnel to successfully complete the proposed studies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
7P01HL112730-02
Application #
8683231
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2014-07-21
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
$611,227
Indirect Cost
$251,682
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
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