Figure 6. The IsoLG scavenger 2-HOBA reduces CD4+ T cell activation and ameliorates cardiac dysfunction due to TAC.

Mice were treated orally with the IsoLG scavenger 2-HOBA and the control drug 4-HOBA administered ad libitum in the drinking water (1g/L) for 4 weeks after TAC surgery. (A) CD45⁺MHCII⁺CD11b⁺CD11c⁺ DCs were isolated from the mLNs of wt mice and (B-C) intracellular IsoLG-protein adduct accumulation was measured using D11 scfv recombinant antibody, and (D-E) CD80 surface expression was quantified by FACS. (F-G) Total CD62L^loCD44^hi effector CD4+ T cells in the mLNs of wt TAC mice were quantified by FACS. (H-I) IHC was used to determine CD4+ T cell infiltration in frozen LV tissue sections from wt mice. (J-K) Total GFP⁺CD4+ T cells from LV tissues of Nur77^GFP mice treated with 2-HOBA and 4-HOBA were quantified by FACS, 4 weeks after TAC surgery. (L) Transthoracic echocardiography was used to measure LV fractional shortening and (M-N) LV hemodynamic measurements were acquired to determine dP/dt max and dP/dt min, comparing untreated wt Sham mice to wt TAC mice treated with 4-HOBA and 2-HOBA. Scale bars: 100μm. Error bars represent mean ± SEM. (* p<0.05, ** p<0.01; Mann-Whitney test, One-way ANOVA test for comparison of 3 or more groups).