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. 2023 May 22;119(10):1915–1927. doi: 10.1093/cvr/cvad078

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© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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ADAMTS4 activity is increased in the myocardium of rats and patients with cardiac dysfunction. (A) The myocardial amount of full-length fibronectin (240 kDa) and its cleavage fragment (180 kDa) as determined by immunoblots in sham vehicle (n = 6), sham ADAMTS inhibitor (n = 6), AB vehicle (n = 7), and AB ADAMTS inhibitor (n = 17). Representative blots shown. (B) mRNA levels of EDA-fibronectin in myocardial samples from AB rats determined by RT–qPCR in sham vehicle (n = 5), sham ADAMTS inhibitor (n = 6), AB vehicle (n = 7), and AB ADAMTS inhibitor (n = 17). (C) The levels of active ADAMTS1, -4, and -5 proteins, fibronectin 180 kDa fragments, and versican DPEAAE fragments in myocardial samples from explanted human failing hearts (red) compared with healthy donor hearts (blue). Representative blots shown for ADAMTS4 (left), EDA-fibronectin (middle), and versican DPEAAE fragments (right). (D) mRNA levels of ADAMTS1, -4, -5, -9, -15, and -20 in myocardial samples from rats 6 weeks after AB (n = 8) or sham (n = 8). (E) Log2-transformed mRNA levels of ADAMTS1, -4, -5, -9, and -15 in adult human cardiac fibroblasts exposed to stretch (n = 11) compared to control conditions (n = 11). ADAMTS20 levels were not detectable. (F) The levels of ADAMTS1, -4, and -5 protein in myocardial lysates from rats 6 weeks after AB (n = 8) or sham (n = 8) relative to sham group. Bars represent mean ± 1 SD. Groups were compared by one-way ANOVA with planned comparisons followed by Bonferroni correction for the following comparisons: sham vehicle vs. sham ADAMTS inhibitor, sham vehicle vs. AB vehicle, and AB vehicle vs. AB ADAMTS inhibitor. Groups were compared by Student’s t-test for the following comparisons: sham vs. AB, control vs. stretched cells, and donor vs. heart failure patients. P < 0.05 were considered significant and marked with *. AB, aortic banding; EDA, extradomain A; ADAMTS4, a disintegrin and metalloprotease with thrombospondin motif; RT–qPCR, real-time quantitative polymerase chain reaction; DCM, dilated cardiomyopathy.