Recognition of the existence of ventricular myosin isozymes and their regulation by thyroid hormone may provide a biochemical basis for some of the effects of the hormone on myocardial performance. The isozymes, which are referred to as V3, in order of decreasing electrophoretic mobility and ATPase activity, contain the same light chain components, but differ in their heavy chain composition. V1 contains two A heavy chains, V3 two B heavy chains, and V2 one heavy chain of each type. Rabbit and several other mammalian species, including man, have a predominance of the low activity V3 form. The relative proportions of these myosin forms seems consistent with a random association of the heavy chain types. Thyroid hormone administration leads to a predominance of the high activity V1 form of the enzyme, indicating that A chain synthesis has been stimulated and B chain synthesis suppressed. By contrast, the V1 form normally is predominant in rat ventricle; thyroid ablation procedures lead to expression of the V3 form, indicating stimulation of B chain synthesis and suppression of A chain synthesis. Since the ATPase activity of myosin seems closely related to the intrinsic speed of cardiac contraction, a change in myosin isozyme composition from V3 to the V1 may explain the increase in velocity of shortening observed in papillary muscles from thyrotoxic cat and rabbit hearts. Similarly, the switch from V1 to V3 may account for the decrease in performance of hypothyroid rat cardiac muscle. However, in man and other species which normally have a predominance of the V3 form, the reported changes in myocardial performance in hypothyroidism may be related to other factors, including alterations in electro-mechanical coupling, myxedematous infiltration and coronary atherosclerosis. Assessments of LV performance in thyrotoxic subjects and in conscious animal models have indicated that LV wall velocity is not usually greater than normal because of the increase in afterload. Although LV systolic and diastolic dimensions are often increased, ventricular filling pressures remain normal, and there is no evidence of sarcomere stretching or disruption. Acute B-adrenergic blockade has very little influence on any of these alterations in LV performance. Furthermore, animal experiments and computer simulation of the thyrotoxic circulatory system indicate that there are important changes in the peripheral vascular compartments as well as in the heart. These alterations, which include a decrease in peripheral arterial resistance and an increase in Pms, should be regarded as essential features of the high-output state associated with thyrotoxicosis. A change from the V1 to the V3 form also has been shown to occur in the rat ventricle during development, aging, chemically-induced diabetes, and in hemodynamic overload. In some cases, these changes seem to be associated with alterations in plasma thyroid hormone concentration. Also, in diabetes and pressure overload, the changes in myosin isozyme composition can be reversed by thyroxine treatment. Taken together, the experimental data suggest that thyroid hormone may play at least a permissive role in regulating ventricular myosin isozyme expression in many nonthyroidal cardiac conditions. The potential to alter myosin isozyme composition constitutes an important area for future research.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine