Accession Number:

AD1064020

Title:

Fibroblast cardiomyocyte interactions in the pressure overloaded myocardium

Descriptive Note:

[Technical Report, Annual Report]

Corporate Author:

Albert Einstein College of Medicine

Personal Author(s):

• Frangogiannis, Nikolaos

Report Date:

2018-10-01

Pagination or Media Count:

263

Abstract:

Prevailing dogma suggests that fibroblasts exert detrimental actions on the pressure-overloaded heart, by secreting large amounts of extracellular matrix proteins that reduce myocardial compliance and promote diastolic dysfunction. Our exciting preliminary data challenge this concept, demonstrating that activated fibroblasts may protect cardiomyocytes in the pressure-overloaded heart. Fibroblast-specific loss of Smad3 accelerates systolic dysfunction following pressure overload, increasing cardiomyocyte apoptosis and leading to replacement fibrosis. We hypothesize that in the hostile environment of the pressure-overloaded heart, TGF--activated fibroblasts serve a protective role, by directly inducing a pro-survival program in cardiomyocytes exposed to mechanical stress, by secreting cardioprotective mediators, or by depositing specialized extracellular matrix proteins that prevent cardiomyocyte anoikis. This novel hypothesis will be tested using in vivo approaches and in vitro co-culture experiments.

Descriptors:

• health services
• cardiovascular physiological phenomena
• chemical synthesis
• cardiovascular system
• chemistry
• myocardial ischemia
• cardiovascular diagnostic techniques
• cardiovascular surgery
• cardiovascular diseases
• proteins
• cell physiological processes
• stem cells
• peptide growth factors
• blood
• cardiac arrhythmias
• cardiology
• proteomics
• peptides
• cardiomyopathies
• connective tissue

Subject Categories:

• Medicine and Medical Research

Distribution Statement:

[A, Approved For Public Release]