Cardiocyte cytoskeleton in patients with left ventricular pressure overload hypertrophy

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 cm(2)) 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 LS' 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. (J Am Coll Cardiol 2001;37:1080-4) (C) 2001 by the American College of Cardiology.