DOI: 10.1161/01.res.86.8.846. Increased Expression of Cytoskeletal, Linkage, and Extracellular Proteins in Failing Human Myocardium

Increased Expression of Cytoskeletal, Linkage, and Extracellular Proteins in Failing Human Myocardium

10.1161/01.res.86.8.846

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation Research (276)

Abstract

Abstract —Experimental studies have shown that in hypertrophy and heart failure, accumulation of microtubules occurs that impedes sarcomere motion and contributes to decreased ventricular compliance. We tested the hypothesis that these changes are present in the failing human heart and that an entire complex of structural components, including cytoskeletal, linkage, and extracellular proteins, are involved in causing functional deterioration. In explanted human hearts failing because of dilated cardiomyopathy (ejection fraction ≤20%), expression of α- and β-tubulin, desmin, vinculin, fibronectin, and vimentin was determined by Northern and Western blot analysis and compared with normal myocardium from explants not used for transplantation. The mRNA for α- and β-tubulin was increased to 2.4-fold ( P <0.01) and 1.25-fold (NS), respectively; for desmin, 1.2-fold ( P <0.05); for fibronectin, 5-fold ( P <0.001); and for vimentin, 1.7-fold ( P <0.05). Protein levels for α-tubulin increased 2.6-fold ( P <0.02); for β-tubulin, 1.2-fold ( P <0.005); for desmin, 2.1-fold ( P <0.001); for vinculin, 1.2-fold ( P <0.005); for fibronectin, 2.9-fold ( P <0.001); and for vimentin, 1.5-fold ( P <0.005). Confocal microscopy showed augmentation and disorganization of all proteins studied. In combination with the loss of myofilaments and sarcomeric skeleton previously reported, these changes suggest cardiomyocyte remodeling. Increased fibronectin and elevated interstitial cellularity (vimentin labeling) indicate progressive fibrosis. The present results suggest a causative role of cytoskeletal abnormalities and myofilament loss for intrinsic contractile and diastolic dysfunction in failing hearts.

Bibliography

Heling, A., Zimmermann, R., Kostin, S., Maeno, Y., Hein, S., Devaux, B., Bauer, E., KloÌvekorn, W.-P., Schlepper, M., Schaper, W., & Schaper, J. (2000). Increased Expression of Cytoskeletal, Linkage, and Extracellular Proteins in Failing Human Myocardium. Circulation Research, 86(8), 846â853.

Authors 11

Annette Heling (first)
René Zimmermann (additional)
Sawa Kostin (additional)
Yoshi Maeno (additional)
Stefan Hein (additional)
Bruno Devaux (additional)
Erwin Bauer (additional)
Wolf-Peter Klövekorn (additional)
Martin Schlepper (additional)
Wolfgang Schaper (additional)
Jutta Schaper (additional)

References 47 Referenced 250

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Dates

Type	When
Created	13 years, 2 months ago (June 11, 2012, 8:52 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 4:20 p.m.)
Indexed	2 weeks ago (Aug. 23, 2025, 9:46 p.m.)
Issued	25 years, 4 months ago (April 28, 2000)
Published	25 years, 4 months ago (April 28, 2000)
Published Print	25 years, 4 months ago (April 28, 2000)

Funders 0

None

BibTeX

@article{Heling_2000, title={Increased Expression of Cytoskeletal, Linkage, and Extracellular Proteins in Failing Human Myocardium}, volume={86}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.86.8.846}, DOI={10.1161/01.res.86.8.846}, number={8}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Heling, Annette and Zimmermann, René and Kostin, Sawa and Maeno, Yoshi and Hein, Stefan and Devaux, Bruno and Bauer, Erwin and Klövekorn, Wolf-Peter and Schlepper, Martin and Schaper, Wolfgang and Schaper, Jutta}, year={2000}, month=apr, pages={846–853} }

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