Hematopoietic alterations in chronic heart failure patients by somatic mutations leading to clonal hematopoiesis

Abstract

14 (13; 15) PB Hematocrit (%); (n=266) 38 ± 4 41 ± 4 39 ± 4 41 ± 5 0.12 38 (34; 41) 41 (39; 44) 40 (36; 42) 41 (38; 44) PB Thrombocytes (x10 3 /mL); (n=204) 253 ± 76 214 ± 86 196 ± 54 213 ± 61 0.25 248 (186; 279) 197 (162; 222) 184 (150; 248) 210 (168; 253) PB Leukocytes (x10 3 /mL); 7.

The role of clonal haematopoiesis in cardiovascular diseases: epidemiology and experimental studies

“…Further analyses revealed that patients with DNMT3A-mediated clonal haematopoiesis exhibited an elevated Th17/Treg ratio and those with TET2-mediated clonal haematopoiesis exhibited increased circulating CD14 dim CD16 + nonclassical monocytes. These data, and similar analyses of TET2-mediated clonal haematopoiesis in heart failure patients [25], suggest that clonal haematopoiesis confers driver gene-specific effects on the immune system. Although the cause of death was not described in the TAVI study, noncardiac causes of mortality are prevalent in patients who undergo this procedure [26,27], implying that clonal haematopoiesis could have a pleiotropic impact on this population.…”

Translating Evidence from Clonal Hematopoiesis to Cardiovascular Disease: A Systematic Review

“…The relationship between CHIP and chronic inflammation (and subsequent heightened vascular risk) is reported: CHIP causes an increase [71,72] in inflammatory responses and, at the same time, cells carrying CHIP mutations have a fitness advantage under pro-inflammatory conditions [73]. An interesting clinical translation of these findings is the recent observation that suggests a relationship between CHIP and HF [22,74]. Among prominent risk factors in HF genesis, age and systemic inflammation play a prominent role, and the most commonly mutated CHIP-driver genes (TET2 and DNMT3A) are associated with poor prognosis [22,31,39,74] in HF [22,74], even with different effects on the hematopoiesis driven by the two mutated genes.…”

“…An interesting clinical translation of these findings is the recent observation that suggests a relationship between CHIP and HF [22,74]. Among prominent risk factors in HF genesis, age and systemic inflammation play a prominent role, and the most commonly mutated CHIP-driver genes (TET2 and DNMT3A) are associated with poor prognosis [22,31,39,74] in HF [22,74], even with different effects on the hematopoiesis driven by the two mutated genes. It is conceivable that a relationship exists between CHIP, the inflammatory state that worsens as we age [75], and the increased vascular risk in the elderly, with one factor influencing the other and vice-versa [75].…”

A feedback loop: Interactions between Inflammatory Signals and Clonal Hematopoiesis in Cardiovascular Disease

“…Although the presence of CHIP was associated with the incidence of CVD, the total number of peripheral white blood cells did not change (except for the JAK2 mutation driving CHIP) [33]. On the contrary, a recent study showed that in CHIP patients with CHF, TET2 mutations are associated with a net increase of HSPCs in humans with leukocytosis in the BM [38], which is supported by mouse models with conditional TET2 deficiency [39,40].…”