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Effect of Klotho Gene Delivery on Hypertension and Arterial Stiffness in Senescence Accelerated Mice P1 (SAMP1)
Author(s) -
Fan Jun,
Wang Xiuqing,
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.811.8
Subject(s) - klotho , arterial stiffness , senescence , kidney , medicine , blood pressure , biology , endocrinology , immunology
Background & Hypothesis Hypertension and arterial stiffness are aged‐related illness. SAMP1 mice were identified with shortened life span and early signs of senescence. We found that that SAMP1 mice developed hypertension and arterial stiffness compared with age‐matched control (AKR/J) mice (11 months). Secreted klotho expression (SKL) was decreased in the kidney. The purpose of this study is to test the hypothesis that klotho gene delivery attenuates the progression of hypertension and arterial stiffness in SAMP1 mice. Methods & Results. The adeno‐associated virus 2 (AAV2) carrying mouse SKL cDNA (AAV2‐SKL) was constructed for in vivo expression of SKL. Two groups of SAMP1 mice and 2 groups of AKR/J mice received IV delivery of AAV2‐GFP and AAV2‐SKL, respectively. SKL gene delivery attenuated and stopped the further increase in blood pressure and pulse wave velocity in SAMP1 mice. AAV delivery of SKL gene effectively increased renal SKL expression in SAMP1 mice. Expression of TGFβ1, collagen 1, and Scleraxis (transcription factor of collagen synthesis) were increased while the elastin level was decreased in aortas of SAMP1 mice. These changes were reversed by SKL gene delivery. Conclusion Klotho gene delivery effectively prevents the arterial stiffness and hypertension in SAMP1 mice. Klotho deficiency may be involved in senescence‐related arterial stiffening and hypertension.