Key result
ADAMTS5 deficiency in mice on a high-fat diet increased diastolic posterior wall thickness (0.94 vs 0.82 mm; P=0.0056) but did not markedly affect overall cardiac function.
Why the study?
ADAMTS5 is implicated in heart valve development and protects against diet-induced obesity, but its role in cardiac function was unknown.
Does ADAMTS5 deficiency affect cardiac function in mice exposed to standard or high-fat diets?
Does ADAMTS5 deficiency affect cardiac function in mice exposed to standard or high-fat diets?
ADAMTS5 deficiency impairs versican cleavage in the cardiac extracellular matrix and alters some structural parameters on a high-fat diet, but does not significantly affect overall cardiac function.
Answers are grounded in this paper and cite their sources.
Alters LV wall thickness and volume on high-fat diet in mice without affecting systolic function; leaves open ADAMTS5's role in human cardiac remodeling.
The aggrecanase ADAMTS5 (A Disintegrin and Metalloproteinase with ThromboSpondin type 1 motifs, member 5) and the cleavage of its substrate versican have been implicated in the development of heart valves. Furthermore, ADAMTS5 deficiency was shown to protect against diet‐induced obesity, a known risk factor for cardiovascular disease. Therefore, in this study, we investigated the potential role of ADAMTS5 in cardiac function using ADAMTS5‐deficient (Adamts5−/−) mice and their wild‐type (Adamts5+/+) counterparts exposed to a standard‐fat or a high‐fat diet (HFD). Eight‐weeks‐old Adamts5−/− and Adamts5+/+ mice were exposed to each diet for 15 weeks. Cardiac function and electrophysiology were analyzed by transthoracic echocardiogram and electrocardiogram at the end of the study. Cleavage of versican, as detected by the appearance of the DPEEAE neo‐epitope on western blotting with protein extracts, was defective in the heart of HFD‐treated Adamts5−/− as compared with Adamts5+/+ mice. ADAMTS5 deficiency led to statistically significant increases in diastolic posterior wall thickness (0.94 ± 0.023 vs. 0.82 ± 0.036 mm; P = 0.0056) and left ventricle volume (47 ± 4.5 vs. 31 ± 2.5 μL; P = 0.0043) in comparison to Adamts5+/+ mice, but only in animals on a HFD. Cardiac function parameters such as ejection fraction, fractional shortening, and stroke volume were unaffected by ADAMTS5 deficiency or diet. Electrocardiogram analysis revealed no ADAMTS5‐specific changes in either diet group. Thus, in the absence of ADAMTS5, cleavage of versican in the cardiac extracellular matrix is impaired, but cardiac function, even upon exposure to a HFD, is not markedly affected.
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Hemmeryckx et al. (2019) studied Cardiac function. ADAMTS5 deficiency vs. Wild-type (Adamts5+/+) was evaluated on Diastolic posterior wall thickness on high-fat diet (p=0.0056). ADAMTS5 deficiency in mice on a high-fat diet increased diastolic posterior wall thickness (0.94 vs 0.82 mm; P=0.0056) but did not markedly affect overall cardiac function.
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