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Your search keyword '"Alpert, Norman R."' showing total 20 results
Start Over Author "Alpert, Norman R." Publisher lippincott williams & wilkins
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20. Thin-filament-based modulation of contractile performance in human heart failure.

Author

Noguchi T, Hünlich M, Camp PC, Begin KJ, El-Zaru M, Patten R, Leavitt BJ, Ittleman FP, Alpert NR, LeWinter MM, and VanBuren P

Subjects
Actin Cytoskeleton chemistry, Adolescent, Adult, Aged, Animals, Cardiomyopathy, Dilated complications, Chickens, Enzyme Activation drug effects, Female, Heart Failure etiology, Heart Failure therapy, Heart-Assist Devices, Humans, Male, Middle Aged, Myocardial Contraction drug effects, Myocytes, Cardiac enzymology, Myocytes, Cardiac ultrastructure, Phosphorylation, Protein Kinase C physiology, Protein Kinase C beta, Protein Kinase C-alpha, Protein Processing, Post-Translational, Rats, Rats, Sprague-Dawley, Sarcomeres ultrastructure, Tetradecanoylphorbol Acetate pharmacology, Actin Cytoskeleton physiology, Heart Failure physiopathology, Myocardial Contraction physiology, Sarcomeres physiology
Abstract

Background: The contribution of the sarcomere's thin filament to the contractile dysfunction of human cardiomyopathy is not well understood., Methods and Results: We have developed techniques to isolate and functionally characterize intact (native) thin filaments obtained from failing and nonfailing human ventricular tissue. By use of in vitro motility and force assays, native thin filaments from failing ventricular tissue exhibited a 19% increase in maximal velocity but a 27% decrease in maximal contractile force compared with nonfailing myocardium. Native thin filaments isolated from human myocardium after left ventricular assist device support demonstrated a 37% increase in contractile force. Dephosphorylation of failing native thin filaments resulted in a near-normalization of thin-filament function, implying a phosphorylation-mediated mechanism. Tissue expression of the protein kinase C isoforms alpha, beta1, and beta2 was increased in failing human myocardium and reduced after left ventricular assist device support., Conclusions: These novel findings demonstrate that (1) the thin filament is a key modulator of contractile performance in the failing human heart, (2) thin-filament function is restored to near normal levels after LVAD support, and (3) the alteration of thin-filament function in failing human myocardium is mediated through phosphorylation, most likely through activation of protein kinase C.

Published
2004
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