Signaling in pathological &physiological hypertrophy

Project: Research project

Description

DESCRIPTION: (provided by applicant): In response to a wide variety of stimuli,
the heart has the ability to undergo hypertrophic growth. Hypertrophy can be a
physiologic adaptive process during development or in response to exercise. It
is initially adaptive after a pathological stimulus such as pressure overload
but can become maladaptive and is, in fact, a leading predictor of congestive
heart failure. The regulatory feedback systems leading to hypertrophy include a
variety of intracellular factors and signaling cascades. Because the multiple
factors and signaling pathways activated under these conditions are common to
both stimuli, it is critical to understand which common and distinct pathways
lead to pathologic versus physiological hypertrophy. We will use several
transgenic models to help delineate the signaling processes involved in the
progression of pathologic and physiologic hypertrophy. The cardiac phenotype of
a transgenic line lacking an intracellular messenger (MEKKI) of a hypertrophic
signaling cascade will be characterized for its response to pathologic and
physiologic hypertrophic stimuli. In addition, this mouse will be crossed to
three, well-characterized transgenic models for hypertrophic cardiomyopathy
(HCM), which harbor specific mutations in cardiac sarcomeric proteins. One of
these transgenic models has a mutation in the actin-binding domain of the
murine a-myosin heavy chain (a-MHC) and is characterized by a gender specific
increased ventricular mass. Additional models contain a missense mutation of
cardiac troponin T (cTnT) or a truncated cTnT. Interestingly, cTnT mutations
result in significantly decreased ventricular mass. These crossed animals will
be analyzed to determine the integration and contribution of the MEKK1
intracellular pathway to the varied Phenotypes of HCM.
StatusActive
Effective start/end date4/2/02 → …

Funding

  • National Institutes of Health: $48,928.00
  • National Institutes of Health: $38,320.00
  • National Institutes of Health: $46,420.00

Fingerprint

Hypertrophy
Hypertrophic Cardiomyopathy
Phenotype
Troponin T
Mutation
Myosin Heavy Chains
Missense Mutation
Actins
Pressure
Growth
Proteins

ASJC

  • Medicine(all)