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Participation of Immune Cells in Klotho Deficiency‐induced Salt‐sensitive Hypertension
Author(s) -
Zhou Xiaoli,
Lei Han,
Sun Zhongjie
Publication year - 2015
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.29.1_supplement.667.3
Subject(s) - ccr2 , endocrinology , medicine , inflammation , immune system , chemokine , infiltration (hvac) , chemistry , klotho , receptor , kidney , chemokine receptor , immunology , physics , thermodynamics
Objective Klotho (KL) is an aging‐suppressor gene. The purpose of this study is to investigate if immune cells are involved in KL deficiency‐induced salt‐sensitive hypertension. Methods & Results Haploinsufficiency of KL (+/‐) caused spontaneous and persistent increase in blood pressure (BP). Interestingly, the high salt (HS) intake further increased BP and exacerbated hypertension in KL(+/‐) mice, but not in WT mice, suggesting that KL deficiency elicited salt‐sensitive hypertension. The HS loading remarkably increased expression of MCP‐1 and infiltration of macrophages and T cells in kidneys in KL(+/‐) mice. Blockade of CC chemokine receptor 2 (CCR2) by a CCR2‐specific antagonist (INCB3284) abolished the HS‐induced increase in BP in KL(+/‐) mice, suggesting an important role of monocyte chemotaxis in salt‐sensitive hypertension. INCB3284 abolished infiltration of macrophages and T cells in kidneys in KL(+/‐) mice. The expression of Sgk1, NCC and ATP synthase β in kidneys was enhanced by HS loading in KL(+/‐) mice, which can be eliminated by INCB. Blockade of CCR2 abolished HS‐induced renal structural damage and functional impairment in KL(+/‐) mice. Conclusion KL deficiency caused salt‐sensitive hypertension and renal damage via MCP‐1/CCR2‐mediated inflammation and infiltration of macrophages and T cells.