Premium
AMP activated kinase α‐1 subunit knock‐out causes concentric hypertrophy and elevated ventricular function
Author(s) -
Schutrumpf Robert J,
Rubin Leona J,
Hanft Laurin M,
Rindt Hans,
Rovetto Michael J,
McDonald Kerry S,
Fine Deborah M
Publication year - 2009
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.23.1_supplement.989.4
Subject(s) - medicine , endocrinology , contractility , muscle hypertrophy , myocyte , ventricular hypertrophy , myosin , cardiac function curve , glycogen , chemistry , skeletal muscle , heart failure , left ventricular hypertrophy , biochemistry , blood pressure
This study examined the effects of AMP activated kinase (AMPK) α‐1 subunit inactivation (KO) on cardiac morphology and function. Mouse heart function was first assessed by ECG and echocardiography under anesthesia. Hearts were then removed, weighed, and attached to a modified Langendorff apparatus. KO mice had increased heart weight‐to‐body weight ratios (WT = 0.475 ± 0.006 vs KO = 0.615 ± 0.024, P <0.001). Histopathologic evaluation revealed increased myocyte diameter ( P <0.05) but no change in glycogen or connective tissue content in KO mice. Northern and Western blot analysis revealed similar α‐ and β‐ myosin heavy chain content, skeletal actin isoforms, and SERCA2 content between groups. Regarding cardiac function, ECG traces were similar between groups but both fractional shortening (WT = 26.8 ± 1.1% vs KO = 33.1 ± 1.7%, P = 0.005) and ejection fraction (WT = 60.4 ± 1.7% vs KO = 69.4 ± 2.4 %, P = 0.006) were increased in KO mice. Consistent with these data, left ventricular (LV) power output was greater in KO mice (WT = 7.3 ± 2.4 vs KO = 9.5 ± 1.3 g*cm/sec, P = 0.035). Interestingly, LV power increased ~30% after epinephrine in WT hearts but was unchanged in KO hearts. In conclusion, mice lacking the AMPK α‐1 subunit exhibit hypertrophy due, in large part, to enlargement of the myocyte cross sectional area. Hypertrophy was associated with increased contractility and reduced responsiveness to β‐adrenergic stimulation.