Skeletal muscle ultrastructure and function in statin-tolerant individuals

Abstract

Introduction: Statins have well-known benefits on cardiovascular mortality, though up to 15% of patients experience side effects. With guidelines from the American Heart Association, American College of Cardiology, and American Diabetes Association expected to double the number of statin users, the overall incidence of myalgia and myopathy will increase.

Methods: We evaluated skeletal muscle structure and contractile function at the molecular, cellular, and whole tissue levels in 12 statin tolerant and 12 control subjects.

Results: Myosin isoform expression, fiber type distributions, single fiber maximal Ca(2+) -activated tension, and whole muscle contractile force were similar between groups. No differences were observed in myosin-actin cross-bridge kinetics in myosin heavy chain I or IIA fibers.

Conclusions: We found no evidence for statin-induced changes in muscle morphology at the molecular, cellular, or whole tissue levels. Collectively, our data show that chronic statin therapy in healthy asymptomatic individuals does not promote deleterious myofilament structural or functional adaptations.

Keywords: myalgia; myopathy; skeletal muscle; statin; ultrastructure.

© 2015 Wiley Periodicals, Inc.

Figures

Figure 1

Knee extensor isometric and isokinetic torque in controls and subjects taking statins. For group comparisons, data were adjusted for leg fat-free mass. Sample sizes were 12 per group (statin/control), with the exception of 30° and 90° isometric (11/12 statin, 10/12 control) and 180°/s isokinetic (10/12 control). Data are mean ± SE. (P=NS)

Figure 2

Skeletal muscle fiber morphology in controls and subjects taking statins. Data are shown for muscle fiber cross-sectional area average size and relative frequency for MHC I and IIA fibers. Data are mean ± SE. (P=NS)

Figure 3

Skeletal muscle tissue homogenate and single fiber isoform distribution in controls and subjects taking statins. Data are mean ± SE. (P=NS)

Figure 4

Single skeletal muscle fiber maximal Ca2+-activated (pCa 4.5) isometric tension in MHC I and MHC IIA fibers (25°C) in controls and subjects taking statins. The number of fibers evaluated is at the base of each bar. Data are mean ± SE. (P=NS)

Figure 5

Sinusoidal analysis model parameters for maximal Ca2+-activated (pCa 4.5) MHC I and IIA fibers in controls and subjects taking statins (n = 8). The number of fibers studied is shown at the base of each bar on the panel showing myosin attachment time. Definitions for each variable are provided in Methods. (P=NS)

Figure 6

Skeletal muscle myofilament ultrastructure and mitochondrial density in controls and subjects taking statins. Average data are shown for myofibrillar fractional area, A-band length, mitochondrial fractional area, and mitochondrial average size. Data are mean ± SE. (P=NS)