Abstract
Background & ObjectiveThe prevalence of arterial stiffness and hypertension increases with age while the klotho level decreases with age. Compound H stimulates klotho mRNA and protein expression in cell cultures and mouse kidneys. The objective of this study is to asses if compound H affects arterial stiffening and hypertension in aged mice.Methods & Results– Aged mice (24‐30 months) were treated with or without compound H (15 mg/kg, IP daily) for 2 weeks, and adult mice without treatments were used as controls (12 months). Pulse wave velocity (PWV), a direct measure of arterial stiffness, and blood pressure (BP) were increased significantly in aged mice. Compound H reversed aging‐related increases in PWV and BP within 2 weeks of treatment. Compound H effectively increased secreted klotho levels in both kidney and serum. Aging‐related arterial stiffness was associated with increased collagen and decreased elastin contents in the media of aortas. In addition, the expression of MMP2, MM9, and TGFb1 was increased in aortas of aged mice. These changes were attenuated by compound H.ConclusionAging‐related arterial stiffening and hypertension are attributed, at least in part, to klotho deficiency. Compound H increases klotho expression and attenuates arterial stiffening and hypertension in aged mice.
Published Version
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