Abstract 548: Anti-aging Gene Klotho Deficiency Exacerbates High Fat Diet-induced Arterial Stiffening and Hypertension by Downregulation of AMP-activated Protein Kinase
Background: Arterial stiffening and hypertension are progressive aging-related disorders. Klotho is an anti-aging protein but its role in regulation of arterial stiffening and hypertension is poorly understood.
Methods and Results: Heterozygous Klotho deficiency (KL+/-) mice and WT littermate mice were fed on high fat diet (HFD) or normal diet (ND). Pulse wave velocity (PWV), an index of arterial stiffening, was increased in KL+/- mice fed on HFD for 5 weeks. Systolic blood pressure and blood glucose levels increased earlier with greater magnitudes in KL+/- mice fed on HFD. Notably, protein expression of collagen I, Runx2, and TGFβ1 were increased but protein expression of phosphorylated AMPKα (pAMPKα), phosphorylated eNOS (peNOS), and Mn-SOD were decreased in aortas of KL+/- mice fed on HFD for 5 weeks. Interestingly, daily injection of AICAR, an activator of AMPK, abolished the increases in PWV, blood pressure, and blood glucose in KL+/- mice fed on HFD. AICAR not only abolished the downregulation of pAMPKα, peNOS, and Mn-SOD levels but also attenuated the increased levels of collagen I, Runx2, TGFβ1 and superoxide, elastic lamellae breaks, and calcification in aortas in KL+/- mice fed on HFD.
Conclusions: Klohto deficiency promotes HFD-induced arterial stiffening and hypertension. The promoting effects of klotho deficiency on arterial stiffening may be due to downregulation of AMPKα activity.
Author Disclosures: Y. Lin: None. D. Velury: None. Z. Sun: None.
- © 2014 by American Heart Association, Inc.