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Mitochondrial Transcription Factor A & Cardiac Stability
Author(s) -
Kunkel George H.,
Theilen Nicholas,
Jeremic Nevena,
Weber Gregory,
Tyagi Suresh C.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.694.7
Subject(s) - tfam , mitochondrion , biology , medicine , microbiology and biotechnology , chemistry , endocrinology , mitochondrial biogenesis
Heart failure is a functional lack of myocardial performance due to a loss of molecular control over increases in calcium and ROS, resulting in proteolytic degradative advances and cardiac remodeling. Mitochondria are the molecular powerhouse of cells, shifting the sphere of cardiomyocyte stability and performance. Functional mitochondria rely on the molecular abilities of safety factors such as TFAM to maintain physiological parameters. Mitochondrial transcription factor A (TFAM) creates a mitochondrial nucleoid structure around mtDNA, protecting it from mutation, inhibiting NFAT (ROS activator/hypertrophic stimulator), and transcriptionally activating Serca2a to decrease calcium mishandling. Current literature depicts major decreases in TFAM as HF progresses. We aim to assess TFAM function against Calpain 1 and MMP 9 proteolytic activity and its role in cardiac remodeling. To this date, no publication has surfaced describing the effects of aortic banding (AB) as a surgical heart failure model in TFAM‐TG mice. HF models were created via AB in TFAM Transgenic (TFAM‐TG) and C57BLJ‐6 (control) mice. Eight weeks post‐AB, functional and histological analysis revealed a successful banding procedure, resulting in cardiac hypertrophy as observed via echocardiography. Pulse wave and color doppler show increased aortic flow rates as well as turbulent flow at the banding site. Preliminary results of cardiac tissue immuno‐histochemistry of HF‐control mice show decreased TFAM and compensatory increases in Serca2a fluorescent expression, along with increased calpain 1 and MMP9 expression. Protein, RNA, and IHC analysis will further assess TFAM‐TG results post‐banding. Echocardiography show more cardiac stability and functionality in HF induced TFAM‐TG mice than the control counterpart. These preliminary findings, along with our invitro results, suggest that TFAM has molecular therapeutic potential to reduce protease activity. Support or Funding Information The study is supported by NIH Grants HL‐74185 and HL‐108621 to SCT and NIH F31 Grant 1F31HL132527‐01 to GHK