Table 1 |.
Summary of experimental studies in mouse models that reported the effects of the most frequent CH candidate driver mutations on cardiovascular disease
| CH candidate gene | Experimental atherosclerosis phenotype | Experimental cardiac phenotype |
|---|---|---|
| DNMT3A | Accelerated atherosclerosis in Ldlr−/− mice after competitive BMT with 10% Dnmt3a−/− BM cells38 | Worse cardiac function and remodeling in angiotensin-II-infused mice bearing CRISPR-Cas9-edited Dnmt3a in hematopoietic cells39 |
| TET2 | Accelerated atherosclerosis in Ldlr−/− mice after competitive BMT with 10% Tet2−/− or Tet2+/− BM cells25 Accelerated atherosclerosis in Ldlr−/− mice with pan-hematopoietic ablation of Tet2 (ref.14) Accelerated atherosclerosis in Ldlr−/− with myeloid-restricted ablation of Tet2 (refs.14,25) |
Worse cardiac function and remodeling after LAD ligation or TAC in mice subjected to competitive BMT with 10% Tet2−/− or Tet2+/− BM cells54 Worse cardiac function and remodeling after LAD ligation or TAC in mice with myeloid-restricted Tet2 deficiency54 Worse cardiac function and remodeling in angiotensin-II-infused mice bearing CRISPR-Cas9-edited Tet2 in hematopoietic cells39 Worse cardiac function and remodeling in aged mice after non-conditioned BM transfer of Tet2−/− cells55 |
| ASXL1 | Unknown | Unknown |
| JAK2 | Accelerated atherosclerosis in Ldlr−/− mice with pan-hematopoietic expression of Jak2V617F (ref.31) Accelerated atherosclerosis in Ldlr−/− mice with competitive BMT or macrophage-specific expression of Jak2V617F (ref.32) |
Worse cardiac function and remodeling after LAD ligation or TAC in mice with lentivirus-mediated expression of Jak2V617F in myeloid cells56 |
| TP53 | Accelerated atherosclerosis in Ldlr−/− mice after competitive BMT with 20% Trp53−/− BM cells15 | Greater doxorubicin-induced cardiac toxicity in mice after non-conditioned BM transfer of Trp53+/− cells58 |
| PPM1D | Unknown | Worse cardiac function and remodeling in angiotensin-II-infused mice bearing hematopoietic cells expressing a CRISPR-Cas9-edited Ppm1d mutant59 |
LAD, left anterior descending artery; TAC, transverse aortic constriction