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Editorial
. 2024 Oct 11;135(9):951-953.
doi: 10.1161/CIRCRESAHA.124.325364. Epub 2024 Oct 10.

Salt and CHIP: Tet2-CH Aggravates Salt-Sensitive Hypertension in Mice

Caitlyn Vlasschaert  1 , Steven D Crowley  2 , Alexander G Bick  3
Affiliations
Editorial

Salt and CHIP: Tet2-CH Aggravates Salt-Sensitive Hypertension in Mice

Caitlyn Vlasschaert et al. Circ Res. .
No abstract available

Keywords: Editorials; bone marrow; mice; mutation; myeloid cells; risk factors.

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Conflict of interest statement

A.G. Bick is on the scientific advisory board of TenSixteen Bio. The other author reports no conflicts.

Figures

Figure 1.
Figure 1.
Summary of experimental model, main findings, and hypothesized mechanisms. a) Clonal hematopoiesis of indeterminate potential (CHIP) is a condition where at least 4% of all circulating blood cells are derived from a single clonal hematopoietic stem cell population that carries a mutation in a myeloid cancer-associated gene. b) In Polizio et al., CD45.1+ mice received a transfusion of either wild-type (WT) or Tet2−/− CD 45.2+ HSCs, which was permitted to engraft and expand in the bone marrow over a period of 3.5 months. The CD45 dual epitope system enables downstream distinction between progeny of transplanted (CD45.2+) and native (CD45.1+) HSCs. Then, a subset of each of mice from each group were exposed to low-dose Ang II. Blood pressure readings and relative size of the CD45.2+ clonal population were examined before and after Ang II exposure. While there was no difference prior to Ang II infusion, the Tet2-CHIP mice developed higher blood pressure after Ang II exposure compared to the three other groups. Consistent with previous observations, the Tet2−/− CD45.2+ cells exhibited a greater clonal expansion rate than the WT CD45.2+ cells; however, they newly show that this growth rate was further accelerated by treatment with Ang II. c) The proposed mechanism of salt-sensitive hypertension in Ang II-treated Tet2−/− mice includes Ang II-induced production of the CCL5 homing signal by structural cells of the kidney, leading to renal infiltration of Tet2−/− macrophages, which secrete IL-1β due to greater intrinsic NLRP3 inflammasome activation. The locally elevated levels of IL-1β then induce of sodium retention by upregulating sodium-hydrogen exchanger 3 (NHE3) production in the proximal tubule and by promoting activating phosphorylation of the Na-K-2Cl transporter (NKCC2) in the loop of Henle.
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Comment on

References

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