Novel Mechanistic Roles for Ankyrin-G in Cardiac Remodeling and Heart Failure
Michael A. Makara, Jerry Curran, Ellen R. Lubbers, Nathaniel P. Murphy, Sean C. Little, Hassan Musa, Sakima A. Smith, Sathya D. Unudurthi, Murugesan V.S. Rajaram, Paul M.L. Janssen, Penelope A. Boyden, Elisa A. Bradley, Thomas J. Hund and Peter J. Mohler
AnkG cKO Mice Display Increased Ventricular Dysfunction With Age
(A) Kaplan-Meier survival analysis demonstrates increased mortality in AnkG cKO mice beginning at 10 months of age (15-month survival: control 10 of 0; AnkG cKO 3 of 10; *p < 0.05). (B and C) Hematoxylin and eosin staining of control and AnkG cKO hearts demonstrate enlarged hearts with increased heart weight to tibia length ratio (HW/TL) at 12 months of age (D) (p < 0.05). (E and F) M-mode images of control and AnkG cKO hearts demonstrate a significant decrease in ejection fraction in AnkG cKO mice at 12 months (p < 0.05). Imaging illustrates unchanged (G) LVID,d, (H) LVPW,d, and (I) LVAW,d in AnkG cKO at 12 months of age compared with control mice. (J and K) Compared with age-matched control mice, 12-month AnkG cKO hearts display fibrosis and severe vacuolization (scale bars = 100 μm). AnkG = ankyrin-G; cKO = cardiomyocyte-specific knockout; LVAW,d = left ventricular anterior wall end-diastolic dimension; LVID,d = L left ventricular cavity end-diastolic dimension; LVPW,d = left ventricular posterior wall end-diastolic dimension.