Age-Dependent Decline in Cardiac Function in Guanidinoacetate-N-Methyltransferase Knockout Mice.

ABSTRACT:

Aim

Guanidinoacetate N-methyltransferase (GAMT) is the second essential enzyme in creatine (Cr) biosynthesis. Short-term Cr deficiency is metabolically well tolerated as GAMT^-/- mice exhibit normal exercise capacity and response to ischemic heart failure. However, we hypothesized long-term consequences of Cr deficiency and/or accumulation of the Cr precursor guanidinoacetate (GA).

Methods

Cardiac function and metabolic profile were studied in GAMT^-/- mice >1 year.

Results

In vivo LV catheterization revealed lower heart rate and developed pressure in aging GAMT^-/- but normal lung weight and survival versus age-matched controls. Electron microscopy indicated reduced mitochondrial volume density in GAMT^-/- hearts

SUBMITTER: Aksentijevic D 

PROVIDER: S-EPMC6985570 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature