Obstructive hypertrophic cardiomyopathy is associated with reduced expression of vinculin in the intercalated disc

Vlad C. Vasile, William D. Edwards, Steve R. Ommen, Michael John Ackerman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Mutations in the cardiac-specific insert of vinculin, metavinculin, rarely cause hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Subsequently, a missense mutation in the ubiquitously expressed vinculin was discovered in a patient with obstructive HCM. Microscopic examination of both myectomy specimens from patients bearing genetic defects in metavinculin and vinculin showed a marked reduction of vinculin/metavinculin expression in the intercalated disc, but normal expression in the Z-disc. Given that distinct functional domains were altered by the metavinculin and vinculin mutations, we hypothesized that the intercalated disc-specific reduction of vinculin may stem from left ventricular tract obstruction in general rather than rarely observed perturbations in VCL-encoded vinculin. To test this hypothesis, we examined the localization of vinculin/metavinculin in hypertrophied human heart tissue from patients with cardiovascular conditions associated with obstruction and hemodynamic overload using an immunohistochemistry approach. Tissue specimens derived from patients with obstructive HCM and aortic stenosis (AS) showed a universal defect of vinculin/metavinculin expression in the intercalated disc but preserved expression in the cardiac Z-disc, whereas tissue specimens derived from patients with either DCM, hypertensive heart disease (HTN), or pulmonary hypertension (PHTN) exhibited normal expression of vinculin/metavinculin in both the Z- and the intercalated disc despite being associated with hypertrophy. Results of this study suggest that cardiac hypertrophy may be associated with different expression of the marker vinculin/metavinculin depending on the underlying pathophysiology; hemodynamic overload may not affect the localization whereas obstructive disease substantially reduces the expression of vinculin preferentially in the intercalated disc.

Original languageEnglish (US)
Pages (from-to)709-715
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume349
Issue number2
DOIs
StatePublished - Oct 20 2006

Fingerprint

Vinculin
Hypertrophic Cardiomyopathy
Dilated Cardiomyopathy
Hemodynamics
Tissue
Bearings (structural)
Defects
Mutation
metavinculin
Aortic Valve Stenosis
Cardiomegaly
Missense Mutation
Pulmonary Hypertension
Hypertrophy
Heart Diseases
Microscopic examination

Keywords

  • Cardiomyopathy
  • Costamere
  • Hypertrophic cardiomyopathy
  • Hypertrophy
  • Intercalated disc
  • Vinculin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Obstructive hypertrophic cardiomyopathy is associated with reduced expression of vinculin in the intercalated disc. / Vasile, Vlad C.; Edwards, William D.; Ommen, Steve R.; Ackerman, Michael John.

In: Biochemical and Biophysical Research Communications, Vol. 349, No. 2, 20.10.2006, p. 709-715.

Research output: Contribution to journalArticle

@article{5261db96b09440e7938acd77efa6f16a,
title = "Obstructive hypertrophic cardiomyopathy is associated with reduced expression of vinculin in the intercalated disc",
abstract = "Mutations in the cardiac-specific insert of vinculin, metavinculin, rarely cause hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Subsequently, a missense mutation in the ubiquitously expressed vinculin was discovered in a patient with obstructive HCM. Microscopic examination of both myectomy specimens from patients bearing genetic defects in metavinculin and vinculin showed a marked reduction of vinculin/metavinculin expression in the intercalated disc, but normal expression in the Z-disc. Given that distinct functional domains were altered by the metavinculin and vinculin mutations, we hypothesized that the intercalated disc-specific reduction of vinculin may stem from left ventricular tract obstruction in general rather than rarely observed perturbations in VCL-encoded vinculin. To test this hypothesis, we examined the localization of vinculin/metavinculin in hypertrophied human heart tissue from patients with cardiovascular conditions associated with obstruction and hemodynamic overload using an immunohistochemistry approach. Tissue specimens derived from patients with obstructive HCM and aortic stenosis (AS) showed a universal defect of vinculin/metavinculin expression in the intercalated disc but preserved expression in the cardiac Z-disc, whereas tissue specimens derived from patients with either DCM, hypertensive heart disease (HTN), or pulmonary hypertension (PHTN) exhibited normal expression of vinculin/metavinculin in both the Z- and the intercalated disc despite being associated with hypertrophy. Results of this study suggest that cardiac hypertrophy may be associated with different expression of the marker vinculin/metavinculin depending on the underlying pathophysiology; hemodynamic overload may not affect the localization whereas obstructive disease substantially reduces the expression of vinculin preferentially in the intercalated disc.",
keywords = "Cardiomyopathy, Costamere, Hypertrophic cardiomyopathy, Hypertrophy, Intercalated disc, Vinculin",
author = "Vasile, {Vlad C.} and Edwards, {William D.} and Ommen, {Steve R.} and Ackerman, {Michael John}",
year = "2006",
month = "10",
day = "20",
doi = "10.1016/j.bbrc.2006.08.106",
language = "English (US)",
volume = "349",
pages = "709--715",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Obstructive hypertrophic cardiomyopathy is associated with reduced expression of vinculin in the intercalated disc

AU - Vasile, Vlad C.

AU - Edwards, William D.

AU - Ommen, Steve R.

AU - Ackerman, Michael John

PY - 2006/10/20

Y1 - 2006/10/20

N2 - Mutations in the cardiac-specific insert of vinculin, metavinculin, rarely cause hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Subsequently, a missense mutation in the ubiquitously expressed vinculin was discovered in a patient with obstructive HCM. Microscopic examination of both myectomy specimens from patients bearing genetic defects in metavinculin and vinculin showed a marked reduction of vinculin/metavinculin expression in the intercalated disc, but normal expression in the Z-disc. Given that distinct functional domains were altered by the metavinculin and vinculin mutations, we hypothesized that the intercalated disc-specific reduction of vinculin may stem from left ventricular tract obstruction in general rather than rarely observed perturbations in VCL-encoded vinculin. To test this hypothesis, we examined the localization of vinculin/metavinculin in hypertrophied human heart tissue from patients with cardiovascular conditions associated with obstruction and hemodynamic overload using an immunohistochemistry approach. Tissue specimens derived from patients with obstructive HCM and aortic stenosis (AS) showed a universal defect of vinculin/metavinculin expression in the intercalated disc but preserved expression in the cardiac Z-disc, whereas tissue specimens derived from patients with either DCM, hypertensive heart disease (HTN), or pulmonary hypertension (PHTN) exhibited normal expression of vinculin/metavinculin in both the Z- and the intercalated disc despite being associated with hypertrophy. Results of this study suggest that cardiac hypertrophy may be associated with different expression of the marker vinculin/metavinculin depending on the underlying pathophysiology; hemodynamic overload may not affect the localization whereas obstructive disease substantially reduces the expression of vinculin preferentially in the intercalated disc.

AB - Mutations in the cardiac-specific insert of vinculin, metavinculin, rarely cause hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Subsequently, a missense mutation in the ubiquitously expressed vinculin was discovered in a patient with obstructive HCM. Microscopic examination of both myectomy specimens from patients bearing genetic defects in metavinculin and vinculin showed a marked reduction of vinculin/metavinculin expression in the intercalated disc, but normal expression in the Z-disc. Given that distinct functional domains were altered by the metavinculin and vinculin mutations, we hypothesized that the intercalated disc-specific reduction of vinculin may stem from left ventricular tract obstruction in general rather than rarely observed perturbations in VCL-encoded vinculin. To test this hypothesis, we examined the localization of vinculin/metavinculin in hypertrophied human heart tissue from patients with cardiovascular conditions associated with obstruction and hemodynamic overload using an immunohistochemistry approach. Tissue specimens derived from patients with obstructive HCM and aortic stenosis (AS) showed a universal defect of vinculin/metavinculin expression in the intercalated disc but preserved expression in the cardiac Z-disc, whereas tissue specimens derived from patients with either DCM, hypertensive heart disease (HTN), or pulmonary hypertension (PHTN) exhibited normal expression of vinculin/metavinculin in both the Z- and the intercalated disc despite being associated with hypertrophy. Results of this study suggest that cardiac hypertrophy may be associated with different expression of the marker vinculin/metavinculin depending on the underlying pathophysiology; hemodynamic overload may not affect the localization whereas obstructive disease substantially reduces the expression of vinculin preferentially in the intercalated disc.

KW - Cardiomyopathy

KW - Costamere

KW - Hypertrophic cardiomyopathy

KW - Hypertrophy

KW - Intercalated disc

KW - Vinculin

UR - http://www.scopus.com/inward/record.url?scp=33748439075&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748439075&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2006.08.106

DO - 10.1016/j.bbrc.2006.08.106

M3 - Article

VL - 349

SP - 709

EP - 715

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -