Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018801 (
heart failure
)
72,216
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Transverse tubules (t-tubules) are uniquely-adapted membrane invaginations in cardiac myocytes that facilitate the synchronous release of Ca
2+
from internal stores and subsequent myofilament contraction, although these structures become disorganized and rarefied in
heart failure
. We previously observed that
mitsugumin 29
(
Mg29
), an important t-tubule organizing protein in skeletal muscle, was induced in the mouse heart for the first time during dilated cardiomyopathy with
heart failure
. Here we generated cardiac-specific transgenic mice expressing
Mg29
to model this observed induction in the failing heart. Interestingly, expression of
Mg29
in the hearts of Csrp3 null mice (encoding muscle LIM protein, MLP) partially restored t-tubule structure and preserved cardiac function as measured by invasive hemodynamics, without altering Ca
2+
spark frequency. Conversely, gene-deleted mice lacking both
Mg29
and MLP protein showed a further reduction in t-tubule organization and accelerated
heart failure
. Thus, induction of
Mg29
in the failing heart is a compensatory response that directly counteracts the well-characterized loss of t-tubule complexity and reduced expression of anchoring proteins such as junctophilin-2 (Jph2) that normally occur in this disease. Moreover, preservation of t-tubule structure by
Mg29
induction significantly increases the function of the failing heart.
...
PMID:Mitsugumin 29 regulates t-tubule architecture in the failing heart. 2870 55
