Targeted Overexpression of Noncleavable and Secreted Forms of Tumor Necrosis Factor Provokes Disparate Cardiac Phenotypes
Population
Transgenic mice with targeted overexpression of secreted wild-type TNF or a mutated noncleavable…
Comparison
Targeted overexpression of secreted wild-type… vs Comparison between the two transgenic mouse lines
Design
Preclinical
Authors
Discussion
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Member takes
Implication
TNF shedding may drive distinct remodeling phenotypes in mice; leaves open translation to human HF mechanisms or therapies.
Structured PICO
P
Population
Transgenic mice with targeted overexpression of secreted wild-type TNF (MHCsTNF2) or a mutated noncleavable transmembrane form of TNF (MHCmTNF)
I
Intervention
Targeted overexpression of secreted wild-type TNF (MHCsTNF2) or mutated noncleavable transmembrane form of TNF (MHCmTNF); treatment with a broad-based matrix metalloproteinase inhibitor in MHCsTNF2 mice
C
Comparator
Comparison between the two transgenic mouse lines (MHCsTNF2 vs MHCmTNF)
O
Outcome
Left ventricular phenotype (concentric hypertrophy vs dilation) and myocardial collagen contentsurrogate
Posttranslational processing (shedding) of TNF, rather than just its expression, dictates the specific type of adverse cardiac remodeling (dilation vs concentric hypertrophy).
Cite This Study
Diwan et al. (2003) studied this question.