Affiliation:
1. Hopkins Marine Station, Department of Biology, Stanford University, Pacific Grove, CA 93950, USA
2. Environmental and Fisheries Sciences Division, Northwest Fisheries Science Center, National Oceanic and Atmospheric Administration, 2725 Montlake Blvd. E., Seattle, WA 98112, USA
Abstract
Cardiac remodeling results from both physiological and pathological stimuli. Compared to mammals, 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 up-regulation 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 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.
Funder
Prince William Sound Regional Citizens Advisory Council
Publisher
The Company of Biologists
Subject
Insect Science,Molecular Biology,Animal Science and Zoology,Aquatic Science,Physiology,Ecology, Evolution, Behavior and Systematics
Cited by
12 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献