CLINICAL STUDY: VALVE DISEASE
Cardiocyte cytoskeleton in patients with left ventricular pressure overload hypertrophy
Michael R. Zile, MD, FACC*,
G. Randall Green, MD ,
Gregg T. Schuyler, MD, PhD, FACC*,
Gerard P. Aurigemma, MD, FACC ,
D. Craig Miller, MD, FACC and
George Cooper, IV, MD*
* Gazes Cardiac Research Institute, Medical University of South Carolina and the Department of Veterans Affairs Medical Center, Charleston, South Carolina, USA
Department of Cardiovascular and Thoracic Surgery, Stanford University School of Medicine, Stanford, California, USA
Cardiology Division of the University of Massachusetts Medical Center, Worcester, Massachusetts, USA
Manuscript received May 11, 2000;
revised manuscript received October 24, 2000,
accepted December 6, 2000.
Reprint requests and correspondence: Dr. Michael R. Zile, Gazes Cardiac Research Institute, P.O. Box 250773, Medical University of South Carolina, 114 Doughty Street, Charleston, South Carolina 29403
zilem{at}musc.edu
OBJECTIVES
We sought to determine whether the cardiocyte microtubule network densification characteristic of animal models of severe pressure overload cardiac hypertrophy occurs in human patients.
BACKGROUND
In animal models of clinical entities causative of severe right and left ventricular (LV) pressure overload hypertrophy, increased density of the cellular microtubule network, through viscous loading of active myofilaments, causes contractile dysfunction that is normalized by microtubule depolymerization. These linked contractile and cytoskeletal abnormalities, based on augmented tubulin synthesis and microtubule stability, progress during the transition to heart failure.
METHODS
Thirteen patients with symptomatic aortic stenosis (AS) (aortic valve area = 0.6 ± 0.1 cm2) and two control patients without AS were studied. No patient had aortic insufficiency, significant coronary artery disease or abnormal segmental LV wall motion. Left ventricular function was assessed by echocardiography and cardiac catheterization before aortic valve replacement. Left ventricular biopsies obtained at surgery before cardioplegia were separated into free and polymerized tubulin fractions before analysis. Midwall LV fractional shortening versus mean LV wall stress in the AS patients was compared with that in 84 normal patients.
RESULTS
Four AS patients had normal LV function and microtubule protein concentration; six had decreased LV function and increased microtubule protein concentration, and three had borderline LV function and microtubule protein concentration, such that there was an inverse relationship of midwall LV fractional shortening to microtubule protein.
CONCLUSIONS
In patients, as in animal models of severe LV pressure overload hypertrophy, myocardial dysfunction is associated with increased microtubules, suggesting that this may be one mechanism contributing to the development of congestive heart failure in patients with AS.
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Abbreviations and Acronyms
| | AS | = aortic stenosis | | ASE | = American Society of Echocardiography | | LV | = left ventricle, left ventricular | | MAP | = microtubule-associated protein |
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