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Biophys J. 2019 Apr 23;116(8):1386-1393. doi: 10.1016/j.bpj.2019.03.010. Epub 2019 Mar 22.

A Matched-Filter-Based Algorithm for Subcellular Classification of T-System in Cardiac Tissues.

Author information

1
Department of Chemistry, University of Kentucky, Lexington, Kentucky; Department of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky. Electronic address: dfco222@g.uky.edu.
2
Department of Chemistry, University of Kentucky, Lexington, Kentucky; Department of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky.
3
Nora Eccles Harrison Cardiovascular Research and Training Institute & Department of Bioengineering, University of Utah, Salt Lake City, Utah.
4
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway; K.G. Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, Oslo, Norway.

Abstract

In mammalian ventricular cardiomyocytes, invaginations of the surface membrane form the transverse tubular system (T-system), which consists of transverse tubules (TTs) that align with sarcomeres and Z-lines as well as longitudinal tubules (LTs) that are present between Z-lines in some species. In many cardiac disease etiologies, the T-system is perturbed, which is believed to promote spatially heterogeneous, dyssynchronous Ca2+ release and inefficient contraction. In general, T-system characterization approaches have been directed primarily at isolated cells and do not detect subcellular T-system heterogeneity. Here, we present MatchedMyo, a matched-filter-based algorithm for subcellular T-system characterization in isolated cardiomyocytes and millimeter-scale myocardial sections. The algorithm utilizes "filters" representative of TTs, LTs, and T-system absence. Application of the algorithm to cardiomyocytes isolated from rat disease models of myocardial infarction (MI), dilated cardiomyopathy induced via aortic banding, and sham surgery confirmed and quantified heterogeneous T-system structure and remodeling. Cardiomyocytes from post-MI hearts exhibited increasing T-system disarray as proximity to the infarct increased. We found significant (p < 0.05, Welch's t-test) increases in LT density within cardiomyocytes proximal to the infarct (12 ± 3%, data reported as mean ± SD, n = 3) versus sham (4 ± 2%, n = 5), but not distal to the infarct (7 ± 1%, n = 3). The algorithm also detected decreases in TTs within 5° of the myocyte minor axis for isolated aortic banding (36 ± 9%, n = 3) and MI cardiomyocytes located intermediate (37 ± 4%, n = 3) and proximal (34 ± 4%, n = 3) to the infarct versus sham (57 ± 12%, n = 5). Application of bootstrapping to rabbit MI tissue revealed distal sections comprised 18.9 ± 1.0% TTs, whereas proximal sections comprised 10.1 ± 0.8% TTs (p < 0.05), a 46.6% decrease. The matched-filter approach therefore provides a robust and scalable technique for T-system characterization from isolated cells through millimeter-scale myocardial sections.

PMID:
30979553
PMCID:
PMC6486484
[Available on 2020-04-23]
DOI:
10.1016/j.bpj.2019.03.010

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