Key result
ALDH2 deficiency exacerbated TAC-induced cardiac fibrosis and dysfunction by increasing bone marrow fibroblast progenitor cell mobilization and myocardial homing.
Why the study?
ALDH2 deficiency exacerbates pressure overload-induced heart failure, but the role and mechanisms of cardiac fibrosis in this process remain largely unknown.
ALDH2 deficiency exacerbates pressure overload-induced cardiac fibrosis and dysfunction by promoting bone marrow fibroblast progenitor cell mobilization via ROS accumulation and the SDF-1/CXCR4 axis.
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ALDH2 may be a therapeutic target to limit fibrosis; leaves open translation from animal models to patients.
Cardiac fibrosis is a common feature of various cardiovascular diseases. Previous studies showed that acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbated pressure overload-induced heart failure. However, the role and mechanisms of cardiac fibrosis in this process remain largely unknown. This study aimed to investigate the effect of ALDH2 deficiency on cardiac fibrosis in transverse aortic constriction (TAC) induced pressure overload model in mice. Echocardiography and histological analysis revealed cardiac dysfunction and enhanced cardiac fibrosis in TAC-operated animals; ALDH2 deficiency further aggravated these changes. ALDH2 chimeric mice were generated by bone marrow (BM) transplantation of WT mice into the lethally irradiated ALDH2KO mice. The proportion of circulating fibroblast progenitor cells (FPCs) and ROS level in BM after TAC were significantly higher in ALDH2KO mice than in ALDH2 chimeric mice. Furthermore, FPCs were isolated and cultured for in vitro mechanistic studies. The results showed that the stem cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) axis played a major role in the recruitment of FPCs. In conclusion, our research reveals that increased bone marrow FPCs mobilization and myocardial homing contribute to the enhanced cardiac fibrosis and dysfunction induced by TAC in ALDH2 KO mice via exacerbating accumulation of ROS in BM and myocardial SDF-1 expression.
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Li et al. (2019) studied Cardiac fibrosis. ALDH2 deficiency vs. Wild-type / ALDH2 chimeric mice was evaluated on Cardiac fibrosis, cardiac dysfunction, and proportion of circulating fibroblast progenitor cells. ALDH2 deficiency exacerbated TAC-induced cardiac fibrosis and dysfunction by increasing bone marrow fibroblast progenitor cell mobilization and myocardial homing.
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