Cardiac remodeling in response to embryonic crude oil exposure involves unconventional NKX family members and innate immunity genes.

Autor:	Gardner LD; Hopkins Marine Station, Department of Biology, Stanford University, Pacific Grove, CA 93950, USA., Peck KA; Environmental and Fisheries Sciences Division, Northwest Fisheries Science Center, National Oceanic and Atmospheric Administration, 2725 Montlake Blvd. E., Seattle, WA 98112, USA., Goetz GW; Environmental and Fisheries Sciences Division, Northwest Fisheries Science Center, National Oceanic and Atmospheric Administration, 2725 Montlake Blvd. E., Seattle, WA 98112, USA., Linbo TL; Environmental and Fisheries Sciences Division, Northwest Fisheries Science Center, National Oceanic and Atmospheric Administration, 2725 Montlake Blvd. E., Seattle, WA 98112, USA., Cameron JR; Environmental and Fisheries Sciences Division, Northwest Fisheries Science Center, National Oceanic and Atmospheric Administration, 2725 Montlake Blvd. E., Seattle, WA 98112, USA., Scholz NL; Environmental and Fisheries Sciences Division, Northwest Fisheries Science Center, National Oceanic and Atmospheric Administration, 2725 Montlake Blvd. E., Seattle, WA 98112, USA., Block BA; Hopkins Marine Station, Department of Biology, Stanford University, Pacific Grove, CA 93950, USA., Incardona JP; Environmental and Fisheries Sciences Division, Northwest Fisheries Science Center, National Oceanic and Atmospheric Administration, 2725 Montlake Blvd. E., Seattle, WA 98112, USA john.incardona@noaa.gov.
Jazyk:	angličtina
Zdroj:	The Journal of experimental biology [J Exp Biol] 2019 Nov 12; Vol. 222 (Pt 21). Date of Electronic Publication: 2019 Nov 12.
DOI:	10.1242/jeb.205567
Abstrakt:	Cardiac remodeling results from both physiological and pathological stimuli. Compared with mammalian hearts, fish hearts show a broader array of remodeling changes in response to environmental influences, providing exceptional models for dissecting the molecular and cellular bases of cardiac remodeling. We recently characterized a form of pathological remodeling in juvenile pink salmon ( Oncorhynchus gorbuscha ) in response to crude oil exposure during embryonic cardiogenesis. In the absence of overt pathology (cardiomyocyte death or inflammatory infiltrate), cardiac ventricles in exposed fish showed altered shape, reduced thickness of compact myocardium and hypertrophic changes in spongy, trabeculated myocardium. Here, we used RNA sequencing to characterize molecular pathways underlying these defects. In juvenile ventricular cardiomyocytes, antecedent embryonic oil exposure led to dose-dependent upregulation of genes involved in innate immunity and two NKX homeobox transcription factors not previously associated with cardiomyocytes, nkx2.3 and nkx3.3 Absent from mammalian genomes, the latter is largely uncharacterized. In zebrafish embryos, nkx3.3 demonstrated a potent effect on cardiac morphogenesis, equivalent to that of nkx2.5 , the primary transcription factor associated with ventricular cardiomyocyte identity. The role of nkx3.3 in heart growth is potentially linked to the unique regenerative capacity of fish and amphibians. Moreover, these findings support a cardiomyocyte-intrinsic role for innate immune response genes in pathological hypertrophy. This study demonstrates how an expanding mechanistic understanding of environmental pollution impacts - i.e. the chemical perturbation of biological systems - can ultimately yield new insights into fundamental biological processes. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2019. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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