Structural and Enzymatic Comparison of Human Cardiac Muscle Myosins Isolated from Infants, Adults, and Patients with Hypertrophic Cardiomyopathy

Abstract

A B S T R A C T Human cardiac ventricular myosins were prepared from autopsy samples from nine adults, seven infants, and from surgical specimens from seven patients undergoing left ventricular septal myectomy for obstructive hypertrophic cardiomyopathy. Infant myosin differed from adult myosin in two important characteristics: (a) t-30% of the 27,000-dalton myosin light chain is replaced by a 28,000-dalton light chain, and (b) the actin-activated myosin MgATPase activity of infant myosin is significantly lower than that of adult myosin (64 nmol phosphate released/mg myosin per min vs. 124 nmol/mg per min at 37°C). The K+-EDTA ATPase activity of the myosin measured in 0.5M KC1 is also lower in infants (1,210 nmol/mg per min vs. 620 nmol/mg per min at 37°C), but the Ca++-activated ATPase is not significantly different. There were no differences in enzymatic activity between the normal adult and cardiomyopathic myosins.A detailed study was performed to investigate possible variations in the structure of the myosin heavy chain in infant, adult, and cardiomyopathic samples. There were no significant differences between infant and normal adult, or between normal adult and cardiomyopathic myosins seen in pyrophosphate polyacrylamide gel electrophoresis, or peptide mapping using alpha-chymotrypsin, papain, or cyanogen bromide to generate peptides.These results suggest that isoenzymes of human ventricular myosin do not exist for the myosin heavy chain in the specimens examined from infants, adults, and patients with obstructive hypertrophic cardiomyopaDr. Schier's present address is

Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium.

“…Rodents undergo a developmental change from ␤-to ␣-MHC as the dominant isoform, and then during hypertrophy or myocardial failure express as the dominant isoform ␤-MHC (41). Since most previous studies (35,36,38,39) had suggested that human ventricular myocardium does not express a biologically significant amount of ␣-MHC and therefore does not undergo an isoform change in hypertrophy or failure, the MHC isogene expression data in this report and in our companion paper (43) were unanticipated. In fact, as originally designed the only reason MHC isogene expression was measured in the current study was to provide a method of normalization of other mRNAs.…”

“…In humans, ␣-and ␤-MHC are closely related isogenes positioned sequentially on chromosome 14 (34). Although a substantial amount of ␣-MHC is present in human atrial myocardium (35)(36)(37), in human ventricular myocardium most previous studies have not detected significant (Ͼ 10%) ␣-MHC expression at the protein or mRNA levels (35,36,38,39). Our data indicate that there is substantial expression of ␣-MHC mRNA in nonfailing ventricular myocardium, and then a profound decrease in expression in myocardial failure.…”

Characterization of Actin and Myosin in the Developing Stomach

“…In response to chronic heart overload in rodents, a shift in MHC occurred with an increase in the slow MHC isoform V3 and a decrease in the fast MHC isoform VI (26), Similar changes have been noted in the human atrial smooth muscle but not in ventricular muscle (7,23). A change in MHC isoform distribution has been seen in the rodent ventricle with hypothyroidism and in skeletal muscle after hypertroph y of chicken slow muscle from repeated use (19,27).…”

Myofibrillar remodelling in cardiac hypertrophy, heart failure and cardiomyopathies

“…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).…”