Increases of desmin and α-actinin in mouse cardiac myofibrils as a response to diastolic dysfunction.

Abstract

Up-regulation of desmin has been reported in cardiac hypertrophy and failure but the pathophysiological cause and significance remain to be investigated. By examining genetically modified mouse models representative for diastolic or systolic heart failure, we found significantly increased levels of desmin and α-actinin in the myofibrils of hearts with impaired diastolic function but not hearts with weakened systolic function. The increased desmin and α-actinin are mainly found in myofibrils at the Z-disks. Two weeks of transverse aortic constriction (TAC) induced increases of desmin and α-actinin in mouse hearts of occult diastolic failure but not in wild type or transgenic mouse hearts with mildly lowered systolic function or with increased diastolic function. The chronic or TAC-induced increase of desmin showed no proportional increase in phosphorylation, implicating an up-regulated expression rather than a decreased protein turnover. The data demonstrate a novel early response specifically to diastolic heart failure, indicating a function of the Z-disk in the challenging clinical condition of heart failure with preserved ejection fraction (HFpEF).