Altered Expression of Disintegrin Metalloproteinases and Their Inhibitor in Human Dilated Cardiomyopathy
Population
Myocardium from patients with dilated cardiomyopathy, hypertrophic obstructive cardiomyopathy, and…
Design
Cross-sectional
Authors
Discussion
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Member takes
Implication
May indicate ADAM10/15-driven integrin shedding in dilated cardiomyopathy; leaves open whether this pathway is therapeutically actionable.
Structured PICO
P
Population
Myocardium from patients with dilated cardiomyopathy (n=20), hypertrophic obstructive cardiomyopathy (n=5), and nonfailing donor hearts (n=7). Paired samples (n=10) were obtained before left ventricular assist device insertion and at transplantation.
C
Comparator
Nonfailing donor hearts (n=7) and hypertrophic obstructive cardiomyopathy samples (n=5); paired samples before and after hemodynamic unloading via LVAD.
O
Outcome
Expression of ADAM10, ADAM12, ADAM15, and ADAM17, TIMP-3, and integrin receptors beta1D and beta3, as well as integrin shedding (ratio of integrin cleavage products to intact protein abundance).surrogate
ADAM10 and ADAM15 are upregulated and TIMP-3 is downregulated in human dilated cardiomyopathy, suggesting a mechanism for cardiac dilatation via integrin shedding that could serve as a future therapeutic target.
Cite This Study
Fedak et al. (2006) studied this question.