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The role of CD8+ T lymphocytes, IP‐10 and MMP12 in hypertension
Author(s) -
Thabet Salim Riad,
Wu Jing,
Blinder Yelena,
Chen Wei,
Madhur Meena S,
Gongora Maria C,
Weyand Cornelia,
Harrison David G
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.640.37
We have previously shown that T cells are essential for the development of hypertension. In the present study, we define a potential pathway linking T cells to the development of hypertension. We find that hypertension stimulates CD8+ but not CD4+ T lymphocytes to produce the inflammatory cytokines IFN‐ã and TNF‐á. IFN‐ã inducible protein‐10 (IP10−/−) mice are protected against angiotensin II‐induced hypertension as compared to C57BL/6J mice (SBPs: 143 ± 6 mmHg vs. 176 ± 4 mmHg respectively). Oxidative stress, TNF‐ã and IP10 increase expression of MMPs, and we find that aortic MMP12 expression is enhanced 4‐fold by angiotensin II. This activation of MMP12 is essential for the development of hypertension, in that MMP12−/− mice are protected against angiotensin II‐induced hypertension compared to mice lacking MMP9 or wild type C57BL/6J mice (SBPs: 122 ± 4 mmHg vs. 172 ± 6 mmHg and 174 ± 5 respectively). In addition, these studies identify a previously undefined role for CD8+ cells, IP10 and MMP12 in the genesis of hypertension and support the role of CD8+ T lymphocyte activation in elastin degradation in this common disease. Future studies are needed to elucidate the mechanisms of CD8+ T cell activation and their relationship with different components of the vascular extracellular matrix.