Relationship between myosin isoenzyme composition, hemodynamics, and myocardial structure in various forms of human cardiac hypertrophy.

Abstract

Hemodynamic and angiographic parameters, muscle fiber diameter, nonmuscle tissue content, and myosin light chain isoform composition were determined in the left ventricle of nine patients with primary (four with hypertrophic, five with dilated cardiomyopathy) and 27 patients with secondary hypertrophy (11 with aortic regurgitation, 16 with aortic stenosis), nine patients with coronary heart disease, and seven controls. In various forms of hypertrophy, a new atrial-like light chain 1 occurred in two-dimensional electrophoresis of total tissue homogenates amounting up to 29% of total light chain 1. Total light chain 1 content remained constant in all groups when related to tropomyosin. The mean content of this atrial light chain 1 was highest in dilated cardiomyopathy (12.1%), less in cases with pressure (6.4%) and volume overload (2.9%), but as low in hypertrophic cardiomyopathy (0.3%) as in controls (0.4%). In cases with coronary heart disease without prior infarction, it was lower (0.6%) than with infarction (1.9%). Its occurrence was not affected by digoxin administration. In ventricular myocardium, an atrial-like light chain 2 was never observed. Peptide patterns after limited proteolytic digestion of isolated myosin heavy chains from cases with pressure overload and hypertrophic cardiomyopathy were identical to those from controls. The content of the atrial-like light chain 1 was not correlated to either muscle fiber diameter or nonmuscle tissue content, both of which were increased in all hypertrophy groups. In individual cases, no firm correlation could be established between atrial-like light chain 1 content and various parameters of ventricular load and function. However, a significant correlation resulted when the mean values of atrial-like light chain 1 content of each disease group were related to the respective mean values of peak circumferential wall stress (r = 0.96). Thus, the shift of myosin light chain 1 isoforms in ventricle seems to characterize biochemically the hypertrophy process induced by mechanical stress.

Loss ofProx1in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy

“…Moreover, a splice variant of cardiac TnT that resembles Tnnt3 causes DCM in multiple animal models (34) and is expressed in failing human hearts (35). Overexpression of the fast-twitch Myl1 gene also alters the contractile function of the heart (36) and is up-regulated exclusively in patients with DCM (37). Consequently, contractile defects arising from the de-repression of fast-twitch skeletal muscle gene expression, coupled with the persistence of myocardial sarcomeric defects from the embryo (7), likely underpins the development of DCM in the Prox1 mutant mice.…”

Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies

“…The expression of this isoform was detected in the hypertrophied human ventricle (17). The hypertrophied right ventricle of children with tetralogy of Fallot (18) and the hemodynamically overloaded left ventricle of patients with valvular disease (19,20) also express a large amount of ALC 1 . It appears that these changes are potentially reversible because surgical intervention with subsequent normalization of the hemodynamic state decreases ALC 1 expression (20).…”

“…The formation of such a molecule in the overloaded heart reduces contractility by lowering the rate of interaction between the actin and myosin filaments. However, this concept is not generally accepted, especially due to controversial data obtained from the diseased human heart (19,33,(47)(48)(49)(50)(51).…”

“…Although ALC 1 becomes re-expressed in the overloaded human ventricle (17,19,20,22,74), β-MHC may combine with either ALC 1 and/or ventricular light chain 1 (VLC 1 ) to form two homodimers and one heterodimer in diseased human ventricles (23). The main consequence of ALC 1 re-expression in the ventricle is the increase of Ca 2+ sensitivity of the contractile apparatus (74).…”

Troponin T Expression in Normal and Pressure-Loaded Fetal Sheep Heart

“…Often, in the adult models, the developing heart. The prenatal cardiac muscle can increase reexpression of fetal or perinatal isoforms is observed (5)(6)(7). cell number in response to stress, whereas the adult heart Additionally, changes in the levels of expression of enzymes increases cell mass.…”