Mechanotransduction in cardiac hypertrophy and failure
#MMPMID25858069
Lyon RC
; Zanella F
; Omens JH
; Sheikh F
Circ Res
2015[Apr]; 116
(8
): 1462-1476
PMID25858069
show ga
Cardiac muscle cells have an intrinsic ability to sense and respond to mechanical
load through a process known as mechanotransduction. In the heart, this process
involves the conversion of mechanical stimuli into biochemical events that induce
changes in myocardial structure and function. Mechanotransduction and its
downstream effects function initially as adaptive responses that serve as
compensatory mechanisms during adaptation to the initial load. However, under
prolonged and abnormal loading conditions, the remodeling processes can become
maladaptive, leading to altered physiological function and the development of
pathological cardiac hypertrophy and heart failure. Although the mechanisms
underlying mechanotransduction are far from being fully elucidated, human and
mouse genetic studies have highlighted various cytoskeletal and sarcolemmal
structures in cardiac myocytes as the likely candidates for load transducers,
based on their link to signaling molecules and architectural components important
in disease pathogenesis. In this review, we summarize recent developments that
have uncovered specific protein complexes linked to mechanotransduction and
mechanotransmission within the sarcomere, the intercalated disc, and at the
sarcolemma. The protein structures acting as mechanotransducers are the first
step in the process that drives physiological and pathological cardiac
hypertrophy and remodeling, as well as the transition to heart failure, and may
provide better insights into mechanisms driving mechanotransduction-based
diseases.
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