What does this research mean for the field?

TRPM2 knockout mice develop greater cardiac hypertrophy and fibrosis under isoproterenol stress and exhibit reduced ANP secretion compared to wild-type mice. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The study aims to determine the role of TRPM2 in regulating ANP secretion during β-adrenergic stress.

January 10, 2026Cells0 citationsOpen Access

Atrial TRPM2 Channel-Mediated Ca2+ Influx Regulates ANP Secretion and Protects Against Isoproterenol-Induced Cardiac Hypertrophy and Fibrosis

TNTomohiro NumataJikei University School of Medicine HTHideaki TagashiraKyushu University of Health and Welfare KSKaori Sato-NumataAkita University

Key Result

TRPM2 knockout mice developed greater cardiac hypertrophy and fibrosis under isoproterenol stress and exhibited reduced ANP secretion compared to wild-type mice.

Key Points

The study aims to determine the role of TRPM2 in regulating ANP secretion during β-adrenergic stress.
Compared wild-type and TRPM2 knockout mice under β-adrenergic stress induced by isoproterenol.
Utilized echocardiography, histology, RT-PCR, electrophysiology, Ca2+ imaging, ELISA, and atrial RNA-seq.
Measured physiological responses to determine heart function and ANP levels.
TRPM2−/− mice exhibited increased cardiac hypertrophy, fibrosis, and systolic dysfunction compared to wild-type mice.
Wild-type mice showed significant induction of the Nppa gene and higher circulating ANP levels under isoproterenol treatment.
Exogenous ANP treatment reduced dysfunction, hypertrophy, and fibrosis in TRPM2−/− mice, indicating TRPM2's vital role in cardioprotection.

Structured PICO

Does TRPM2 channel deletion worsen isoproterenol-induced cardiac hypertrophy and fibrosis in mice?

Population

Male C57BL/6J wild-type (WT) and TRPM2 knockout (TRPM2−/−) mice (8–12 weeks old)

Intervention

Isoproterenol (ISO) to induce β-adrenergic stress; exogenous atrial natriuretic peptide (ANP)

Comparator

Wild-type (WT) mice receiving the same isoproterenol (ISO) treatment

Outcome

Cardiac hypertrophy, fibrosis, and systolic dysfunctionsurrogate

TRPM2 channels are essential for the cardioprotective endocrine response via ANP secretion to mitigate β-adrenergic stress-induced cardiac remodeling.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Transient receptor potential melastatin 2 (TRPM2) channel is a Ca2+-permeable, redox-activated cardiac ion channel protective in ischemia–reperfusion, but whether it regulates atrial endocrine output under stress is unclear. Here, we investigated whether TRPM2 contributes to the atrial natriuretic peptide (ANP) response during β-adrenergic stimulation. We compared how male C57BL/6J wild-type (WT) and TRPM2 knockout (TRPM2−/−) mice (8–12 weeks old) respond to β-adrenergic stress induced by isoproterenol (ISO) using echocardiography, histology, RT-PCR, electrophysiology, Ca2+ imaging, ELISA, and atrial RNA-seq. We detected abundant Trpm2 transcripts in WT atria and measured ADP-ribose (ADPr)-evoked currents and hydrogen peroxide (H2O2)-induced Ca2+ influx characteristic of TRPM2; these were absent in TRPM2−/− cells. Under the ISO-induced hypertrophic model, TRPM2−/− mice developed greater cardiac hypertrophy, fibrosis, and systolic dysfunction compared with WT mice. Atrial bulk RNA-seq showed significant induction of Nppa (ANP precursor gene) in WT + ISO, accompanied by higher circulating ANP; TRPM2−/− + ISO showed blunted Nppa and ANP responses. ISO-treated TRPM2−/− mice exhibited more blunt responses, in both Nppa transcripts and circulating ANP levels. Exogenous ANP attenuated ISO-induced dysfunction, hypertrophy, and fibrosis in TRPM2−/− mice, suggesting that TRPM2 is needed for the cardioprotective endocrine response via ANP to control stress-induced β-adrenergic remodeling.

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