Prevention of Cardiac Hypertrophy in Mice by Calcineurin Inhibition

Overview

Journal Science

Specialty Science

Date 1998 Sep 11

PMID 9733519

Citations 115

Authors

M A Sussman

H W Lim

N Gude

T Taigen

E N Olson

J Robbins

M C Colbert

A Gualberto

D F Wieczorek

J D Molkentin

Affiliations

Soon will be listed here.

Abstract

Hypertrophic cardiomyopathy (HCM) is an inherited form of heart disease that affects 1 in 500 individuals. Here it is shown that calcineurin, a calcium-regulated phosphatase, plays a critical role in the pathogenesis of HCM. Administration of the calcineurin inhibitors cyclosporin and FK506 prevented disease in mice that were genetically predisposed to develop HCM as a result of aberrant expression of tropomodulin, myosin light chain-2, or fetal beta-tropomyosin in the heart. Cyclosporin had a similar effect in a rat model of pressure-overload hypertrophy. These results suggest that calcineurin inhibitors merit investigation as potential therapeutics for certain forms of human heart disease.

Citing Articles

Calcineurin-NFAT dynamics correspond to cardiac remodeling during aortic banding and debanding, mimicking aortic valve replacement.

Lunde I, Skrbic B, Sjaastad I, Christensen G, Carlson C, Tonnessen T Front Mol Med. 2024; 2:980717.

PMID: 39086965 PMC: 11285616. DOI: 10.3389/fmmed.2022.980717.

The potential roles of exosomes in pathological cardiomyocyte hypertrophy mechanisms and therapy: A review.

Zhang L, Xie F, Zhang F, Lu B Medicine (Baltimore). 2024; 103(17):e37994.

PMID: 38669371 PMC: 11049793. DOI: 10.1097/MD.0000000000037994.

Stage-specific therapy for hypertrophic cardiomyopathy.

Argiro A, Zampieri M, Marchi A, Cappelli F, Del Franco A, Mazzoni C Eur Heart J Suppl. 2023; 25(Suppl C):C155-C161.

PMID: 37125313 PMC: 10132571. DOI: 10.1093/eurheartjsupp/suad042.

Cardiovascular effects of immunosuppression agents.

Elezaby A, Dexheimer R, Sallam K Front Cardiovasc Med. 2022; 9:981838.

PMID: 36211586 PMC: 9534182. DOI: 10.3389/fcvm.2022.981838.

Protein Kinase D1 Regulates Cardiac Hypertrophy, Potassium Channel Remodeling, and Arrhythmias in Heart Failure.

Bossuyt J, Borst J, Verberckmoes M, Bailey L, Bers D, Hegyi B J Am Heart Assoc. 2022; 11(19):e027573.

PMID: 36172952 PMC: 9673734. DOI: 10.1161/JAHA.122.027573.