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Updated: Mar 16, 2026
Transverse Aortic Constriction in Mice
Published on: April 21, 2010
Resistance to pathologic cardiac hypertrophy and reduced expression of CaV1.2 in Trpc3-depleted mice
Jung Woo Han1, Young Ho Lee2, Su-In Yoen2
1Department of Pharmacology and Brain Korea, 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
Abstract:
Sustained elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) reprograms cardiovascular cell fate, leading to cellular hypertrophy via Ca(2+)-calmodulin/calcineurin (Cn)/NFAT activation. Accumulating evidence suggests that transient receptor potential canonical (Trpc) channels play important roles in the development of pathologic cardiac hypertrophy. Here, we demonstrated that Trpc3 mediates pathologic cardiac hypertrophy in neurohumoral elevation via direct regulation of CaV1.2 expressions. Elevated PE (phenylephrine) was maintained in mice by continuous infusion using an osmotic pump. Wild-type (WT) mice, but not Trpc3 (-/-) showed a sudden decrease in blood pressure (BP) or death following elevation of BP under conditions of elevated PE. Trpc3 (-/-) mesenteric artery showed decreased PE-stimulated vasoconstriction. Analysis of morphology, function, and pathologic marker expression revealed that PE elevation caused pathologic cardiac hypertrophy in WT mice, which was prevented by deletion of Trpc3. Interestingly, protection by Trpc3 deletion seemed to be a result of reduced cardiac CaV1.2 expressions. Basal and PE induced increased expression of protein and mRNA of CaV1.2 was decreased in Trpc3 (-/-) heart. Accordingly, altered expression of CaV1.2 was observed by knockdown or stimulation of Trpc3 in cardiomyocytes. These findings suggest that Trpc3 is a mediator of pathologic cardiac hypertrophy not only through mediating part of the Ca(2+) influx, but also through control of CaV1.2 expressions.
Insights
Transient Receptor Potential Canonical 3 (Trpc3) channels mediate pathological cardiac hypertrophy by regulating CaV1.2 expression. Deleting Trpc3 prevents hypertrophy, offering a potential therapeutic target for cardiovascular disease.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Ion Channel Function
Background:
- Sustained intracellular calcium ([Ca(2+)]i) elevation reprograms cardiovascular cell fate, promoting hypertrophy via Ca(2+)-calmodulin/calcineurin/NFAT signaling.
- Transient Receptor Potential Canonical (Trpc) channels are implicated in the development of pathological cardiac hypertrophy.
Purpose of the Study:
- To investigate the role of Trpc3 in mediating pathological cardiac hypertrophy induced by neurohumoral elevation.
- To elucidate the mechanism by which Trpc3 contributes to cardiac hypertrophy, specifically its regulation of CaV1.2 expression.
Main Methods:
- Utilized a mouse model with sustained phenylephrine (PE) infusion to induce cardiac hypertrophy.
- Compared wild-type (WT) and Trpc3 knockout (Trpc3-/-) mice, assessing blood pressure, vasoconstriction, cardiac morphology, function, and marker expression.
- Investigated CaV1.2 expression at protein and mRNA levels in hearts and cardiomyocytes from WT and Trpc3-/- mice, including knockdown and stimulation experiments.
Main Results:
- Trpc3 deletion prevented PE-induced pathological cardiac hypertrophy in WT mice.
- Trpc3-/- mice exhibited reduced blood pressure decrease and mortality under elevated PE conditions compared to WT.
- Trpc3 deletion significantly reduced both basal and PE-induced expression of cardiac CaV1.2 at the protein and mRNA levels.
Conclusions:
- Trpc3 acts as a key mediator of pathological cardiac hypertrophy.
- Trpc3 regulates cardiac hypertrophy not only through calcium influx but also by controlling CaV1.2 expression.
- Targeting Trpc3 may offer a novel therapeutic strategy for preventing or treating cardiac hypertrophy.
