Myofibril orientation as a metric for characterizing heart disease

• DOI: 10.1016/j.bpj.2022.01.009
• Publication Date: 2022-01-13T00:38:43Z
• Authors: Weikang Ma; Henry Gong; Vivek Jani; Kyoung Hwan Lee; Maicon Landim-Vieira; Maria Papadaki; Jose R. Pinto; M. Imran Aslam; Anthony Cammarato; Thomas Irving
• Keywords: Myofibril; Myofilament

Myocyte disarray is a hallmark of many cardiac disorders. However, the relationship between alterations in orientation individual myofibrils and myofilaments to disease progression has been largely underexplored. This oversight predominantly because paucity methods for objective quantitative analysis. Here, we introduce novel, less-biased approach quantify myofibrillar myofilament muscle under near-physiological conditions demonstrate its superiority as compared with conventional histological assessments. Using small-angle x-ray diffraction, first investigated changes at increasing sarcomere lengths permeabilized, relaxed, wild-type mouse myocardium from left ventricle by assessing angular spread 1,0 equatorial reflection (angle σ). At length 1.9 μm, angle σ was 0.23 ± 0.01 rad, decreased 0.19 rad 2.1 further 0.15 2.3 μm (p < 0.0001). Angle significantly larger R403Q, MYH7 hypertrophic cardiomyopathy model, porcine (0.24 rad) (0.14 0.005 rad; p 0.0001), well human heart failure tissue (0.19 0.006 when nonfailing samples (0.17 0.007 = 0.01). These data indicate that diseased suffers greater disorientation healthy controls. Finally, showed conventional, histology-based analysis can be subject user bias and/or sampling error lead false positives. Our method directly avoids artifacts introduced approaches assess myocyte only indirectly evaluate orientation, provides precise metric phenotypically characterizing myocardium. The ability obtain excellent diffraction patterns frozen new tool investigating structural anomalies associated diseases.