Overcontraction and excess actin filaments. Basic elements of hypertrophic cardiomyopathy

Area of Science:

• Cardiology
• Cell Biology
• Biophysics

Background:

• Hypertrophic cardiomyopathy (HCM) is a complex cardiac disease characterized by myocardial hypertrophy.
• Understanding the subcellular mechanisms underlying HCM contraction is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the ultrastructural changes in myocardial fibers of patients with hypertrophic cardiomyopathy.
• To elucidate the role of actin and myosin filament arrangement in the contractile dysfunction observed in HCM.

Main Methods:

• Endomyocardial biopsies were obtained from the right ventricular septum of three HCM patients.
• Biopsied tissues were examined using electron microscopy, focusing on both longitudinal and transverse sections of myocardial fibers.

Main Results:

• Transverse sections revealed disarray in actin filament arrangement and expansion of the myosin lattice, indicative of overcontraction.
• The number of actin filaments per hexagon ranged from 7 to 14, with only one case exceeding 12.
• Overcontraction was concluded to cause progressive deviation of actin filaments during systole due to double overlap, leading to self-impeding contraction.

Conclusions:

• Myocardial overcontraction, evidenced by actin filament disarray and myosin lattice expansion, is a significant ultrastructural finding in hypertrophic cardiomyopathy.
• This overcontraction may lead to impaired myocardial function through a "self-impeding contraction" mechanism.
• An excess of actin filaments might play a functional role in balancing unequal contractile forces within HCM fibers.