Abstract 613: Mitochondrial Hydrogen Peroxide In T Cell Activation In Hypertension
Substantial evidence demonstrates that mitochondrial reactive oxygen species and adoptive immunity are critical in the development of hypertension. Our initial observations indicated that T cells isolated from hypertensive mice produced more cellular and mitochondrial hydrogen peroxide (H2O2) compared to those from normotensive animals, 98% and 48% respectively. We hypothesized that mitochondrial H2O2 plays a regulatory role in T cell activation in hypertension. We used RAG1-/- male mice that lack lymphocytes and modulated mitochondrial H2O2 by adoptive transfer of T cells with various mitochondrial H2O2 levels. RAG1-/- mice received T cells from wild type mice (RAG1-/-+WT) or mice expressing catalase in mitochondria (RAG1-/-+mCat). Adoptive transfer of T cells was performed 3 weeks prior to Ang II infusion (490 ng/kg/min). Our data show that inhibition of mitochondrial H2O2 specifically in T cells prevents hypertension. When challenged with angiotensin II, systolic BP in RAG1-/-+WT mice rose to 174 mmHg (+/-7.7) which was similar to values observed in WT mice (173 mmHg +/-12). However, scavenging mitochondrial H2O2 in T cells significantly (P<0.01) blunted the hypertensive response in RAG1-/-+mCat mice (135 mmHg +/-9.7). Interestingly, hypertension led to accumulation of CD45+/CD3+ T cell in aorta and kidney of WT mice and RAG1-/- mice that received WT T cells but not those receiving T cells expressing mitochondria catalase. Next, we investigated the mitochondrial metabolism in T cells isolated from hypertensive mice and found that hypertension reduced T cell respiration by 67% and increased ATP production by 54%. These changes were reversed by scavenging mitochondrial H2O2. Our data also show that the rates of glutamine intake and lactate production in T cells are dependent on mitochondrial oxygen species. We propose that mitochondrial hydrogen peroxide plays an important role in regulating T cell metabolism and functions in hypertension.
Author Disclosures: R.R. Nazarewicz: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Modest; AHA 14SDG20410081. M.A. Saleh: None. J. Wu: None. S. Dikalov: None. D.G. Harrison: None.
- © 2014 by American Heart Association, Inc.