Key result
Cardiomyocyte-restricted deficiency of IRS1 attenuated pressure overload-induced cardiac hypertrophy and prevented heart failure, whereas IRS2 deficiency exacerbated left ventricular dysfunction.
Why the study?
Pressure overload cardiac hypertrophy and heart failure are associated with hyperinsulinemia, but whether IRS1 and IRS2 exert divergent effects on pressure overload-induced LV remodeling was unknown.
Does cardiomyocyte-restricted deficiency of IRS1 or IRS2 differentially affect pressure overload-induced left ventricular remodeling?
Population
CIRS1KO, CIRS2KO, and WT mice subjected to TAC, and failing human hearts
Comparison
CIRS1KO vs CIRS2KO vs WT mice subjected to TAC
Design
Preclinical animal and human tissue study
Authors
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Signals caution against broad IRS targeting in HF; leaves open isoform-specific windows pending clinical translation.
Does cardiomyocyte-restricted deficiency of IRS1 or IRS2 differentially affect pressure overload-induced left ventricular remodeling?
Absolute Event Rate: 18.6% vs 54.4%
p-value: p=<0.05
IRS1 and Akt1 act as critical signaling nodes mediating left ventricular remodeling in response to pressure overload, demonstrating divergent roles for IRS1 and IRS2 in cardiac hypertrophy.
Riehle et al. (2020) studied Heart failure and left ventricular remodeling. Cardiomyocyte-restricted deficiency of IRS1 (CIRS1KO) vs. Wild-type (WT) and IRS2-deficient (CIRS2KO) mice was evaluated on Cardiac hypertrophy (Heart weight/tibia length ratio percent increase after TAC) (p=<0.05). Cardiomyocyte-restricted deficiency of IRS1 attenuated pressure overload-induced cardiac hypertrophy and prevented heart failure, whereas IRS2 deficiency exacerbated left ventricular dysfunction.
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