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Editorial
. 2023 Apr 1;324(4):H414-H416.
doi: 10.1152/ajpheart.00075.2023. Epub 2023 Feb 10.

Calcium "stress" adds a third hit in driving heart failure with preserved ejection fraction

Kyohei Fujita  1 , Matthew W Ellis  1 , Farah Sheikh  1
Affiliations
Editorial

Calcium "stress" adds a third hit in driving heart failure with preserved ejection fraction

Kyohei Fujita et al. Am J Physiol Heart Circ Physiol. .
No abstract available

Keywords: L-type calcium channel; cardiac hypertrophy; cardiac muscle; heart failure with preserved ejection fraction; histone deacetylase.

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Conflict of interest statement

F.S. is a cofounder and shareholder of Papillon Therapeutics, Inc., as well as consultant and shareholder of LEXEO Therapeutics, Inc.

Figures

Figure 1.
Figure 1.
Overview of “3 hit” model for heart failure with preserved ejection fraction (HFpEF). Left: systemic stressors include a high-fat diet, leading to metabolic stress and overworked mitochondria, and Nω-nitro-l-arginine methyl ester (l-NAME)-induced hypertensive vascular stress, leading to elevated blood pressure. Each of these indirectly acts as a constitutive stressor on heart function. In the FVB/NJ mouse model, these “2 hits” are insufficient to cause development of the heart failure with preserved ejection fraction (HFpEF) phenotype. Right: addition of a cardiomyocyte-specific calcium stressor via expression of the β2a-subunit of the L-type calcium channel (Cavβ2a) constitutes a “3rd hit,” leading to development of HFpEF together with the systemic stressors. HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) alleviates the HFpEF phenotype in the 3-hit mouse model by attenuating the hypertrophic phenotype driven by calcium influx. A: increased Cavβ2a expression leads to higher levels of Ca2+ flux through the channel, inducing cardiomyocyte calcium stress. B: normal β2a expression leads to lower Ca2+ flux through the channel.
See this image and copyright information in PMC

Comment on

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