Dataset Information

Novel Mechanistic Roles for Ankyrin-G in Cardiac Remodeling and Heart Failure.

ABSTRACT: Ankyrin polypeptides are intracellular proteins responsible for targeting cardiac membrane proteins. Here, the authors demonstrate that ankyrin-G plays an unexpected role in normal compensatory physiological remodeling in response to myocardial stress and aging; the authors implicate disruption of ankyrin-G in human heart failure. Mechanistically, the authors illustrate that ankyrin-G serves as a key nodal protein required for cardiac myofilament integration with the intercalated disc. Their data define novel in vivo mechanistic roles for ankyrin-G, implicate ankyrin-G as necessary for compensatory cardiac physiological remodeling under stress, and implicate disruption of ankyrin-G in the development and progression of human heart failure.

SUBMITTER: Makara MA

PROVIDER: S-EPMC6234521 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel Mechanistic Roles for Ankyrin-G in Cardiac Remodeling and Heart Failure.

Makara Michael A MA Curran Jerry J Lubbers Ellen R ER Murphy Nathaniel P NP Little Sean C SC Musa Hassan H Smith Sakima A SA Unudurthi Sathya D SD Rajaram Murugesan V S MVS Janssen Paul M L PML Boyden Penelope A PA Bradley Elisa A EA Hund Thomas J TJ Mohler Peter J PJ

JACC. Basic to translational science 20181001 5

Ankyrin polypeptides are intracellular proteins responsible for targeting cardiac membrane proteins. Here, the authors demonstrate that ankyrin-G plays an unexpected role in normal compensatory physiological remodeling in response to myocardial stress and aging; the authors implicate disruption of ankyrin-G in human heart failure. Mechanistically, the authors illustrate that ankyrin-G serves as a key nodal protein required for cardiac myofilament integration with the intercalated disc. Their dat ...[more]

PMID: 30456339

Similar Datasets

Project description:Background:Left ventricular assist devices (LVADs) have revolutionized and improved the care of the sickest heart failure (HF) patients, and it is imperative that they receive appropriate ventricular unloading. Assessing this critical parameter with current methodologies (labs, imaging) is usually suboptimal in this patient population. Hence it is imperative to elucidate the molecular underpinnings involved in ventricular unloading. We have previously identified the cytoskeletal protein ?II spectrin as an essential nodal protein involved in post-translational targeting and ?II spectrin protein levels are significantly altered in multiple forms of human and animal HF. We therefore hypothesized that the ?II spectrin pathway would play a critical role in LVAD remodeling. Methods:Human heart failure samples were obtained from patients undergoing heart transplantation. Wild type (WT) mice and our previously validated ?II spectrin conditional knock out (?II cKO) mice were used for animal experiments. Transaortic constriction (TAC) was performed on WT mice. Protein expression was assessed via immunoblots, and protein interactions were assessed with co-immunoprecipitation. Transcriptome analysis was performed using isolated whole hearts from control adult WT mice (n = 3) compared to ?II cKO spectrin mice (n = 3). Results:We report that hearts from mice selectively lacking ?II spectrin expression in cardiomyocytes displayed altered transcriptional regulation of cardiac ankyrin repeat protein (CARP). Notably, CARP protein expression is increased after TAC. Additionally, our findings illustrate that prior to LVAD support, CARP levels are elevated in HF patients compared to normal healthy controls. Further, for the first time in a LVAD population, we show that elevated CARP levels in HF patients return to normal following LVAD support. Conclusion:Our findings illustrate that CARP is a dynamic molecule that responds to reduced afterload and stress, and has the potential to serve as a prognostic biomarker to assess for an adequate response to LVAD therapy.

Dataset Information

Novel Mechanistic Roles for Ankyrin-G in Cardiac Remodeling and Heart Failure.

Publications

Novel Mechanistic Roles for Ankyrin-G in Cardiac Remodeling and Heart Failure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets