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Profilin modulates sarcomeric organization and mediates cardiomyocyte hypertrophy.

Kooij V, Viswanathan MC, Lee DI, Rainer PP, Schmidt W, Kronert WA, Harding SE, Kass DA, Bernstein SI, Van Eyk JE, Cammarato A - Cardiovasc. Res. (2016)

Bottom Line: Mechanistically, we found that profilin-1 regulates hypertrophy, in part, through activation of the ERK1/2 signalling cascade.Elevated profilin levels resulted in elongated sarcomeres, myofibrillar disorganization, and sarcomeric disarray, which correlated with impaired muscle function.Our results identify novel roles for profilin as an important mediator of cardiomyocyte hypertrophy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, MD, USA National Heart and Lung Institute, Imperial College London, 4th floor, ICTEM, Hammersmith Campus, Du Cane Road, London W12 0NN, UK v.kooij@imperial.ac.uk.

No MeSH data available.


Related in: MedlinePlus

Cardiomyocyte-specific overexpression of profilin in Drosophila induces cardiomyopathy. (A) Representative M-mode kymograms generated from high-speed videos of beating control, Pfn_1, and Pfn_2 heart tubes. DD, diastolic diameter; SD, systolic diameter; HP, heart period. (B) Semi-automated optical heartbeat analysis from flies overexpressing profilin via the HG4 cardiac-specific driver revealed significant reductions in heart period and increased cardiac dimensions relative to control (n = 28–30, *P < 0.05, **P < 0.01 and ***P < 0.001; Kruskal–Wallis test with Dunn's post hoc test for HP and SD analysis; one-way ANOVA with the Bonferroni post hoc test for DD analysis).
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CVW050F2: Cardiomyocyte-specific overexpression of profilin in Drosophila induces cardiomyopathy. (A) Representative M-mode kymograms generated from high-speed videos of beating control, Pfn_1, and Pfn_2 heart tubes. DD, diastolic diameter; SD, systolic diameter; HP, heart period. (B) Semi-automated optical heartbeat analysis from flies overexpressing profilin via the HG4 cardiac-specific driver revealed significant reductions in heart period and increased cardiac dimensions relative to control (n = 28–30, *P < 0.05, **P < 0.01 and ***P < 0.001; Kruskal–Wallis test with Dunn's post hoc test for HP and SD analysis; one-way ANOVA with the Bonferroni post hoc test for DD analysis).

Mentions: To investigate cardiomyocyte-restricted effects of increased profilin expression in vivo, and to assess whether elevated profilin quantity is sufficient to alter contractile performance and/or cardiac dimensions in a tissue-specific manner, two independent transgenic fly lines (UAS-Pfn_1 and UAS-Pfn_2) were crossed with flies harbouring the heart-specific Hand-GAL4 (HG4) driver (Figure 2A). Cardiac-restricted overexpression of profilin in the progeny resulted in significantly reduced heart periods (HG4 > Pfn_1 464 ± 23 ms, n = 31; HG4 > Pfn_2 421 ± 21 ms, n = 30), which indicated increased heart rate, compared with control (553 ± 30 ms, n = 28; Figure 2B). Diastolic diameters were significantly enlarged in HG4 > Pfn_1 (66 ± 2 μm, n = 31) and HG4 > Pfn_2 (71 ± 1 μm, n = 30) relative to control (60 ± 1 μm, n = 28) flies, as were systolic diameters in HG4 > Pfn_2 (43 ± 1 μm, n = 30) compared with control (38 ± 2 μm, n = 28; Figure 2B). Knockdown of profilin in cardiomyocytes (HG4 > PfnRNAi) was maladaptive and resulted in lethality, as flies did not eclose from their puparia. These data suggest that profilin is essential for adult Drosophila cardiac development, and that its overexpression induces a phenotype reminiscent of eccentric hypertrophy.36Figure 2


Profilin modulates sarcomeric organization and mediates cardiomyocyte hypertrophy.

Kooij V, Viswanathan MC, Lee DI, Rainer PP, Schmidt W, Kronert WA, Harding SE, Kass DA, Bernstein SI, Van Eyk JE, Cammarato A - Cardiovasc. Res. (2016)

Cardiomyocyte-specific overexpression of profilin in Drosophila induces cardiomyopathy. (A) Representative M-mode kymograms generated from high-speed videos of beating control, Pfn_1, and Pfn_2 heart tubes. DD, diastolic diameter; SD, systolic diameter; HP, heart period. (B) Semi-automated optical heartbeat analysis from flies overexpressing profilin via the HG4 cardiac-specific driver revealed significant reductions in heart period and increased cardiac dimensions relative to control (n = 28–30, *P < 0.05, **P < 0.01 and ***P < 0.001; Kruskal–Wallis test with Dunn's post hoc test for HP and SD analysis; one-way ANOVA with the Bonferroni post hoc test for DD analysis).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4836629&req=5

CVW050F2: Cardiomyocyte-specific overexpression of profilin in Drosophila induces cardiomyopathy. (A) Representative M-mode kymograms generated from high-speed videos of beating control, Pfn_1, and Pfn_2 heart tubes. DD, diastolic diameter; SD, systolic diameter; HP, heart period. (B) Semi-automated optical heartbeat analysis from flies overexpressing profilin via the HG4 cardiac-specific driver revealed significant reductions in heart period and increased cardiac dimensions relative to control (n = 28–30, *P < 0.05, **P < 0.01 and ***P < 0.001; Kruskal–Wallis test with Dunn's post hoc test for HP and SD analysis; one-way ANOVA with the Bonferroni post hoc test for DD analysis).
Mentions: To investigate cardiomyocyte-restricted effects of increased profilin expression in vivo, and to assess whether elevated profilin quantity is sufficient to alter contractile performance and/or cardiac dimensions in a tissue-specific manner, two independent transgenic fly lines (UAS-Pfn_1 and UAS-Pfn_2) were crossed with flies harbouring the heart-specific Hand-GAL4 (HG4) driver (Figure 2A). Cardiac-restricted overexpression of profilin in the progeny resulted in significantly reduced heart periods (HG4 > Pfn_1 464 ± 23 ms, n = 31; HG4 > Pfn_2 421 ± 21 ms, n = 30), which indicated increased heart rate, compared with control (553 ± 30 ms, n = 28; Figure 2B). Diastolic diameters were significantly enlarged in HG4 > Pfn_1 (66 ± 2 μm, n = 31) and HG4 > Pfn_2 (71 ± 1 μm, n = 30) relative to control (60 ± 1 μm, n = 28) flies, as were systolic diameters in HG4 > Pfn_2 (43 ± 1 μm, n = 30) compared with control (38 ± 2 μm, n = 28; Figure 2B). Knockdown of profilin in cardiomyocytes (HG4 > PfnRNAi) was maladaptive and resulted in lethality, as flies did not eclose from their puparia. These data suggest that profilin is essential for adult Drosophila cardiac development, and that its overexpression induces a phenotype reminiscent of eccentric hypertrophy.36Figure 2

Bottom Line: Mechanistically, we found that profilin-1 regulates hypertrophy, in part, through activation of the ERK1/2 signalling cascade.Elevated profilin levels resulted in elongated sarcomeres, myofibrillar disorganization, and sarcomeric disarray, which correlated with impaired muscle function.Our results identify novel roles for profilin as an important mediator of cardiomyocyte hypertrophy.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, MD, USA National Heart and Lung Institute, Imperial College London, 4th floor, ICTEM, Hammersmith Campus, Du Cane Road, London W12 0NN, UK v.kooij@imperial.ac.uk.

No MeSH data available.


Related in: MedlinePlus