Key result
CD44 knockout or inhibition protects mice from TAC-induced LV hypertrophy, fibrosis, and dysfunction.
Why the study?
Inflammation contributes to heart failure progression, and CD44 regulates tissue inflammation and fibrosis, but its role and cellular mechanism in pressure overload-induced heart failure were unclear.
Does inhibition of CD44 attenuate pressure overload-induced cardiac and lung inflammation, fibrosis, and heart failure progression in mice?
Does inhibition of CD44 attenuate pressure overload-induced cardiac and lung inflammation, fibrosis, and heart failure progression in mice?
Inhibition of CD44 signaling attenuates cardiac and lung inflammation, fibrosis, and heart failure progression in pressure overload mouse models, suggesting a potential therapeutic target for HF.
CD44 inhibition attenuated TAC-induced HF progression in mice; leaves open therapeutic translation pending human trials.
Background Inflammation contributes to heart failure (HF) development and progression. CD44 is a member of the hyaluronate receptor family of cell adhesion molecules, which regulates tissue inflammation and fibrosis through modulating macrophage and lymphocyte migration and homing in several diseases. Here we evaluated the role and cellular mechanism of CD44 in regulating transverse aortic constriction (TAC)-induced HF development and progression in mice. Methods and results C57/B6 background CD44 KO and wild type mice (6–8 weeks) were subjected to TAC to evaluate the effect of CD44 on the development of TAC-induced LV hypertrophy and cardiac dysfunction. Due to the rapid response to TAC, Balb/c mice (6–8 weeks) were used to determine the effect of CD44 on the progression of TAC-induced congestive heart failure. We found that CD44 expression is dramatically increased in left ventricular (LV) tissues obtained from HF patients and mice. While CD44 gene knockout (KO) has no detectable effect on cardiac structure and function under control conditions, CD44 KO mice were protected from TAC-induced LV inflammation, fibrosis, hypertrophy, dysfunction, and lung remodeling as compared with wild type mice. In addition, we found that inhibition of CD44 signaling with blocking antibodies (Abs) significantly attenuated the transition from LV failure to lung remodeling, and right ventricular hypertrophy in mice with existing HF. Conclusions These data identify an important role of CD44 in attenuating cardiac and lung inflammation, fibrosis, HF development, and HF progression, suggesting that inhibition of CD44 signaling may be useful in preventing and treating HF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Chinese National Natural Science Foundation Grants and American Heart Association
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Weng et al. (2020) studied Heart failure. CD44 gene knockout or blocking antibodies vs. Wild type mice / control conditions was evaluated on TAC-induced LV inflammation, fibrosis, hypertrophy, dysfunction, and lung remodeling. CD44 gene knockout or inhibition with blocking antibodies protected mice from transverse aortic constriction-induced left ventricular inflammation, fibrosis, hypertrophy, and dysfunction.
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