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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

Adenoviral-mediated overexpression of profilin-1 induces a hypertrophic response in NRVMs. (A) Transcript levels of Pfn1 in NRVMs were significantly higher than control following adenoviral-mediated transfection (n = 12, ***P < 0.001; Student's t-test). (B) Pfn1 overexpression resulted in significantly increased levels of profilin-1 (n = 6, ***P < 0.001; Student's t-test). (C) Elevated Pfn1 expression resulted in increased transcript levels of the hypertrophic markers ANP and BNP (n = 12, *P < 0.05; Student's t-test). (D) NRVMs exhibited significantly larger cellular areas in response to Pfn1 overexpression (n = 33, **P < 0.01; Student's t-test). (E) Representative profilin-1 and α-actinin antibody-stained confocal images of Adv-Control- and Adv-Profilin-1-transfected NRVMs. Scale bar, 15 µm. (F) A ×3.1 zoom of confocal images of Adv-Profilin-1-transfected cells (white box in the merged image). Scale bar, 5 µm.
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CVW050F5: Adenoviral-mediated overexpression of profilin-1 induces a hypertrophic response in NRVMs. (A) Transcript levels of Pfn1 in NRVMs were significantly higher than control following adenoviral-mediated transfection (n = 12, ***P < 0.001; Student's t-test). (B) Pfn1 overexpression resulted in significantly increased levels of profilin-1 (n = 6, ***P < 0.001; Student's t-test). (C) Elevated Pfn1 expression resulted in increased transcript levels of the hypertrophic markers ANP and BNP (n = 12, *P < 0.05; Student's t-test). (D) NRVMs exhibited significantly larger cellular areas in response to Pfn1 overexpression (n = 33, **P < 0.01; Student's t-test). (E) Representative profilin-1 and α-actinin antibody-stained confocal images of Adv-Control- and Adv-Profilin-1-transfected NRVMs. Scale bar, 15 µm. (F) A ×3.1 zoom of confocal images of Adv-Profilin-1-transfected cells (white box in the merged image). Scale bar, 5 µm.

Mentions: Adenoviral-mediated profilin-1 overexpression in NRVMs resulted in significant increases in Pfn1 mRNA (n = 12) and protein (n = 6) levels (Figure 5A and B) compared with controls (Adv-Control). Increased levels of profilin-1 resulted in elevation of the hypertrophic fetal gene markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) (Figure 5C). Additionally, increased cell size, another hallmark of hypertrophy, was measured in cells transfected with Adv-Profilin-1 (6387 ± 317 µm2, n = 33) compared with Adv-Control (5207 ± 260 µm2, n = 33; Figure 5D). Both adenoviruses expressed mCherry under the control of the CMV promoter to determine transfection efficiency. Figure 5E shows representative images of profilin-1 and α-actinin in NRVMs transfected with Adv-Profilin-1 and Adv-Control. Profilin-1 frequently exhibited repetitive occupancy along NRVM myofibrils (Figure 5F). These results indicate that overexpression of profilin-1 in NRVMs is sufficient to induce cellular hypertrophy.Figure 5


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)

Adenoviral-mediated overexpression of profilin-1 induces a hypertrophic response in NRVMs. (A) Transcript levels of Pfn1 in NRVMs were significantly higher than control following adenoviral-mediated transfection (n = 12, ***P < 0.001; Student's t-test). (B) Pfn1 overexpression resulted in significantly increased levels of profilin-1 (n = 6, ***P < 0.001; Student's t-test). (C) Elevated Pfn1 expression resulted in increased transcript levels of the hypertrophic markers ANP and BNP (n = 12, *P < 0.05; Student's t-test). (D) NRVMs exhibited significantly larger cellular areas in response to Pfn1 overexpression (n = 33, **P < 0.01; Student's t-test). (E) Representative profilin-1 and α-actinin antibody-stained confocal images of Adv-Control- and Adv-Profilin-1-transfected NRVMs. Scale bar, 15 µm. (F) A ×3.1 zoom of confocal images of Adv-Profilin-1-transfected cells (white box in the merged image). Scale bar, 5 µm.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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CVW050F5: Adenoviral-mediated overexpression of profilin-1 induces a hypertrophic response in NRVMs. (A) Transcript levels of Pfn1 in NRVMs were significantly higher than control following adenoviral-mediated transfection (n = 12, ***P < 0.001; Student's t-test). (B) Pfn1 overexpression resulted in significantly increased levels of profilin-1 (n = 6, ***P < 0.001; Student's t-test). (C) Elevated Pfn1 expression resulted in increased transcript levels of the hypertrophic markers ANP and BNP (n = 12, *P < 0.05; Student's t-test). (D) NRVMs exhibited significantly larger cellular areas in response to Pfn1 overexpression (n = 33, **P < 0.01; Student's t-test). (E) Representative profilin-1 and α-actinin antibody-stained confocal images of Adv-Control- and Adv-Profilin-1-transfected NRVMs. Scale bar, 15 µm. (F) A ×3.1 zoom of confocal images of Adv-Profilin-1-transfected cells (white box in the merged image). Scale bar, 5 µm.
Mentions: Adenoviral-mediated profilin-1 overexpression in NRVMs resulted in significant increases in Pfn1 mRNA (n = 12) and protein (n = 6) levels (Figure 5A and B) compared with controls (Adv-Control). Increased levels of profilin-1 resulted in elevation of the hypertrophic fetal gene markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) (Figure 5C). Additionally, increased cell size, another hallmark of hypertrophy, was measured in cells transfected with Adv-Profilin-1 (6387 ± 317 µm2, n = 33) compared with Adv-Control (5207 ± 260 µm2, n = 33; Figure 5D). Both adenoviruses expressed mCherry under the control of the CMV promoter to determine transfection efficiency. Figure 5E shows representative images of profilin-1 and α-actinin in NRVMs transfected with Adv-Profilin-1 and Adv-Control. Profilin-1 frequently exhibited repetitive occupancy along NRVM myofibrils (Figure 5F). These results indicate that overexpression of profilin-1 in NRVMs is sufficient to induce cellular hypertrophy.Figure 5

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