Title

Neurogranin regulates calcium-dependent cardiac hypertrophy

Document Type

Article

Publication Date

8-1-2022

Abstract

Intracellular Ca-calmodulin (CaM) signaling plays an important role in Ca-CaM-dependent kinase (CaMKII) and calcineurin (CaN)-mediated cardiac biology. While neurogranin (Ng) is known as a major Ca-CaM modulator in the brain, its pathophysiological role in cardiac hypertrophy has never been studied before. In the present study, we report that Ng is expressed in the heart and depletion of Ng dysregulates Ca homeostasis and promotes cardiac failure in mice. 10-month-old Ng null mice demonstrate significantly increased heart-to-body weight ratios compared to wild-type. Using histological approaches, we identified that depletion of Ng increases cardiac hypertrophy, fibrosis, and collagen deposition near perivascular areas in the heart tissue of Ng null mice. Ca spark experiments revealed that cardiac myocytes isolated from Ng null mice have decreased spark frequency and width, while the duration of sparks is significantly increased. We also identified that a lack of Ng increases CaMKII signaling and periostin protein expression in these mouse hearts. Overall, we are the first study to explore how Ng expression in the heart plays an important role in Ca homeostasis in cardiac myocytes as well as the pathophysiology of cardiac hypertrophy and fibrosis.

Publication Source (Journal or Book title)

Experimental and molecular pathology

First Page

104815

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