Advancing age is a major independent risk factor for cardiovascular disease. The prevalence of specific cardiovascular conditions such as cardiac hypertrophy/failure, atherosclerosis, and inflammation increase with age. Previous studies by the applicant's laboratory illuminated essential roles for KLFs in control of immunity, metabolism, and impact on the cardiovascular system. Nascent observations by the applicant build on the published corpus of work and identify KLFs as a heretofore unappreciated molecular control locus governing both lifespan and healthspan across metazoan life. The current application seeks to (a) determine which mammalian KLFs are linked to aging, (b) determine the effect of manipulating KLF4 on cardiac and vascular healthspan in aging mammals, and (c) determine the effect of manipulating myeloid KLF2 on aging/age-associated inflammatory states. Completion of the outlined work will provide fundamental insights with therapeutic implications regarding aging and age-associated cardiovascular disease.

Public Health Relevance

The prevalence of specific cardiovascular conditions such as cardiac hypertrophy/failure, atherosclerosis, and inflammation increase with age. Recent studies by the applicant have identified a family of factors that control lifespan and healthspan from C. elegans to mammals. The current proposal seeks to fully define the role of KLF in aging and age-associated cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R35)
Project #
5R35HL135789-02
Application #
9418089
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Adhikari, Bishow B
Project Start
2017-02-01
Project End
2024-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106