mAKAP-beta regulation of cardiac myocyte apoptosis and remodeling

Project: Research

Investigators

  • Kristin Tokarski (PI)

Description

Under conditions of stress requiring the heart to increase pumping power, such as pressure overload, striated cardiac myocytes undergo non-mitotic growth which results in increased heart mass. This hypertrophy is accompanied by cell death, or apoptosis, when these stressors are prolonged. The combination of the hypertrophy and apoptosis leads to heart failure. Current treatments for heart failure focus on the symptomatic effects instead of preventing cardiac remodeling and apoptosis. In order to develop better treatments that target the underlying causes of cardiac remodeling, apoptosis, and ultimately decompensation, it is first important to understand the signaling mechanisms behind these events. The aim of this proposal is to understand the role of the scaffold protein mAKAP-beta in cardiac remodeling and apoptosis. mAKAP-beta has been shown to be important for the induction of cardiac hypertrophy under conditions of pressure overload and catecholamine stimulation. Therefore, it is likely that mAKAP-beta induces cardiac remodeling under other forms of stress and is important for the induction of apoptosis. The requirement of mAKAP-beta localization and expression, as well as its binding partners type 3 p90 ribosomal S6 kinase (RSK3) and serum response factor (SRF), for induction of cardiac remodeling and apoptosis after myocardial infarction and under various forms of stress will be investigated. This will be accomplished using primary cell culture of adult rat ventricular myoctyes with mAKAP-beta shRNA mediated knock-out, mAKAP-beta cardiomyocyte specific conditional knock-out mice, and TUNEL staining. The knowledge the proposed studies provide will advance our understanding of pathological signaling within the heart and may provide novel pathways to target for treatment of cardiac hypertrophy and heart failure.
Award amount$62,032.00
Award date01/01/2020
Program typePredoctoral Fellowship
Award ID20PRE35210584
Effective start/end date01/01/202012/31/2021
StatusActive