Fish Heart Research Articles

Effects of in vitro cytochalasin D and hypoxia on mitochondrial energetics and biogenesis, cell signal status and actin/tubulin/Hsp/MMP entity in air-breathing fish heart.

The cardiac actin cytoskeleton has a dynamic pattern of polymerisation. It is uncertain how far actin destabilisation impacts mitochondrial energetics and biogenesis, cell signal status, and structural entities in cardiomyocytes, particularly in hypoxic conditions. We thus tested the in vitro action of cytochalasin D (Cyt D), an inhibitor of actin polymerisation, in hypoxic ventricular explants to elucidate the role of the actin in mitochondrial energetics and biogenesis, cell signals and actin/tubulin/hsps/MMPs dynamics in hypoxic air-breathing fish hearts. The COX activity increased upon Cyt D exposure, whereas hypoxia lowered COX and SDH activities but increased LDH activity. The ROS increased, and NO decreased by Cyt D. COX and LDH activities, and NO content reversed after Cyt D exposure in hypoxic hearts. Cyt D exposure upregulated actin isoform expression (Actc1 and Actb1) but downregulated tubulin isoform (Tedc1). Hypoxia upregulated actin (Acta1a, Actb1, Actb2, Actc1a) tubulin (Tuba, Tubb5, Tedc1, Tubd1) and hsp (Hspa5, Hspa9, Hspa12a, Hspa14, Hspd1, Hsp90) isoform transcript expression and Cyt D in hypoxic hearts reversed these isoform's expression. Hypoxia upregulated Mmp2 and 9 transcript expressions but downregulated Mfn1, Fis1, Nfkb1, Prkacaa, and Aktip expressions, and Cyt D exposure reversed almost all these markers in hypoxic hearts. The data provide novel evidence for the mechanistic role of actin in integrating mitochondrial energetics and biogenesis, cell signal status and actin/tubulin/Hsp/MMP entity, indicating its critical cardioprotective role in defending against hypoxia. Besides proposing an air-breathing fish heart as a model, the study further brings the therapeutic potential of Cyt D towards hypoxia intervention.

Seasonal remodelling of the fish heart alters sensitivity to petrochemical pollutant, 3-methylphenanthrene

Exploitation of offshore oil reserves, heightened traffic in marine transportation routes, and the release of petrochemicals from the thawing of permafrost and glaciers is increasing the bioavailability of polycyclic aromatic hydrocarbons (PAHs) to aquatic organisms. This availability may also change with the seasons as temperature changes accessibility of Arctic transport routes and the degree of land- and ice-melt and thus run-off into coastal ecosystems. Seasonal temperature change also remodels the ion channels in the heart of fish to facilitated preserved cardiac function across a range of temperatures. How this seasonal cardiac remodelling impacts vulnerability to pollutants is currently unknown. In this study we accessed the electrical activity of navaga cod (Eleginus nawaga) ventricular cardiomyocytes under the dual influence of seasonal change and varying concentrations of a pervasive PAH pollutant, 3-methylphenanthrene (3-MP). We used whole-cell patch-clamp to elucidate the effect of various doses of 3-MP on action potential (AP) parameters and the main ion currents (IKr, IK1, INa, ICa) in ventricular cardiomyocytes isolated from navaga cod in winter and summer at the White Sea, close to the Russian Arctic circle. Navaga cod ventricular cardiomyocytes were particularly vulnerable to 3-MP during the winter season. Exposure to 300 nM 3-MP resulted in significant changes in AP duration in winter-acclimatized fish, whereas no such changes were observed in summer-acclimatized fish. The IKr current was the most sensitive to 3-MP, with a winter IC50 of 49.7 nM and a summer IC50 of 53 μM. The INa current also exhibited seasonal shifts in sensitivity to 3-MP, with IC50 values of 2.39 μM in winter-acclimatized fish and 7.73 μM in summer-acclimatized fish. No significant differences were observed in the effect of 3-MP on the peak ICa current, although 3 μM of 3-MP caused a pronounced decrease in charge transferred by ICa (e.g. QCa) in both seasons. The IK1 current was insensitive to 3-MP in both winter and summer fish. These findings highlight how remodelling of the fish heart with changing season alters the potency of PAH pollution. This paper lays the groundwork for future research on the molecular mechanisms that drive the altered seasonal potency of pollutants in navaga cod and other species.

The Effects of Phenanthrene on Electrical Activity in Ventricular Cardiomyocytes of Atlantic Cod (<i>Gadus morhua</i>)

The production of oil on the Arctic shelf and its transport along the Northern Sea Route increase risks of pollution of the ecosystems in the Arctic seas with oil and oil products. Today, polyaromatic hydrocarbons are known as the most toxic oil components, and phenanthrene is predominant in terms of its concentration in oil and physiological effects. Phenanthrene affects the electrical activity of fish heart, but its effects are species-specific. At the same time, the effects of phenanthrene on cardiac function in Arctic fishes, including economically important commercial species, are studied not enough. This study examines the effects of phenanthrene on electrical activity and ionic currents in ventricular myocardium of Atlantic cod (Gadus morhua). The major ionic currents in cod myocardium were IKr, IK1, INa and ICa. Phenanthrene (1 μM) did not affect the duration of action potentials (APs) recorded in isolated cod ventricular cardiomyocytes using patch clamp method. Meanwhile, phenanthrene suppressed rapid delayed rectifier current IKr by 61.33 ± 3.94%, decreasing the repolarization reserve of the myocardium. Phenanthrene did not affect nor the level of resting membrane potential, not background inward rectifier current IK1. Also, application of phenanthrene decreased AP upstroke velocity in cod myocytes, which was due to the suppression of fast sodium current INa. Finally, phenanthrene slightly reduced the amplitude of calcium current ICa and accelerated its inactivation, which overall led to the decrease in ICa charge transfer. Thus, the effects of phenanthrene on cod myocardium at cellular level can be described as potentially proarrhythmic, which makes the populations of cod in Arctic seas vulnerable to pollution of the aquatic environment by oil components after oil spills due to technological disasters.

Basal Expression Profile of Seven Glutathione-S-Transferases (GSTs) Genes in Six Tissues of Tilapia (Oreochromis niloticus) for Polymerase Chain Reaction Array

Study’s Excerpt The differential expression patterns of Glutathione-S-transferase (GST) isoforms in six tissues of Nile tilapia are investigated. Seven specific GST genes are examined across six tissues, and it is determined that the liver, spleen, and intestines are key sites of significant gene expression. GST isoforms could be potentially used as biomarkers for assessing xenobiotic stress in aquatic environments. Full Abstract Because aquatic habitats are being destroyed and biodiversity is declining, xenobiotic pollution of water is a critical environmental problem that has garnered a lot of attention in the past few decades. This study looked at the expression patterns of Glutathione-S-transferases isoforms (GSTMA, GSTO1LA, GSTA, GSTR1, GSTK, GSTT1, and MGST), which are genes involved in xenobiotic metabolism, in Nile tilapia. From adult Nile tilapia, six tissues—liver, spleen, intestines, gills, heart, and muscle—were chosen, and seven genes that were optimised via quantitative polymerase chain reaction (qPCR) were used for validation. Gene expressions were assessed using a PCR array that included duplicate tissues in 96-well qPCR plates, with each gene/plate being assayed six times. Water is used in the remaining wells as no template control (NTC). As reference genes, Pan Ribosomal Protein L3 (RPL3) and Pan 18S ribosomal RNA (18S RNA) were employed. The genes’ basal tissue mRNA expression was measured in each tissue. The muscle was utilised to renormalise the expression levels of all genes throughout the remaining tissues since, under assay’s circumstances the muscle showed very low signal for most of the genes. Using quantitative real-time PCR (qPCR), the result demonstrated widespread differential expression patterns of the seven GST mRNA in the liver, spleen, intestine, gills, heart, and muscle of an untreated fish. However, it was clear that the highest significant expression level of most genes (different GST’s isoforms) was in the liver, followed by the spleen and gut, then the heart and gills compared to muscle (P<0.05). The findings demonstrated widespread differential expression of the GST’s isoforms at basal level and highlighted their utility as biomarkers for xenobiotic stress in aquatic environments.

RACK1 contributes to the upregulation of embryonic genes in a model of cardiac hypertrophy

Receptors for activated C kinases (RACKs) have been shown to coordinate PKC-mediated hypertrophic signalling in mice. However, little information is available on its participation in embryonic gene expression. This study investigated the involvement of RACK1 in the expression of embryonic genes in a zebrafish (ZF) ex vivo heart culture model by using phenylephrine (PE) or a growth factors cocktail (GFs) as a prohypertrophic/regeneration stimulus. Blebbistatin (BL) inhibition has also been studied for its ability to block the signal transduction actions of some PEs. qRT‒PCR and immunoblot analyses confirmed the upregulation of RACK1 in the PE- and GFs-treated groups. BL administration counteracted PE-induced hypertrophy and downregulated RACK1 expression. Immunohistochemical analyses of the heart revealed the colocalization of RACK1 and embryonic genes, namely, Gata4, Wt1, and Nfat2, under stimulation, whereas these genes were expressed at lower levels in the BL treatment group. Culturing ZF heart cells activated via GFs treatment increased the expression of RACK1. The overexpression of RACK1 induced by the transfection of recombinant RACK1 cDNA in ZF heart cells increased the expression of embryonic genes, especially after one week of GFs treatment. In summary, these results support the involvement of RACK1 in the induction of embryonic genes during cardiac hypertrophy/GFs stimulation in a fish heart model, which can be used as an alternative study model for mammals.

Mitochondrial functions and fatty acid profiles in fish heart: an insight into physiological limitations linked to thermal tolerance and age.

Heart failure is among the first major consequences of heat stress in aquatic ectotherms. Mitochondria produce most of the ATP used by the heart and represent almost half of the volume in cardiac cells. It has therefore been hypothesized that mitochondrial dysfunction may be a major cause of heart failure associated with heat stress. The present study aims to investigate if CTmax is linked to the thermal sensitivity of cardiac mitochondria in the three-spined stickleback (Gasterosteus aculeatus), and if it is influenced by heart fatty acid composition and age. To do so, we measured the CTmax of 30 fish. The cardiac mitochondrial oxygen consumption was measured by high resolution respirometry at three temperatures and heart lipid profiles were obtained by gas chromatography (GC) coupled with a flame ionization detector (FID). Fish age was estimated via otolith readings. Fatty acid profiles showed no correlation with CTmax, but EPA levels were higher in older individuals. Mitochondrial respiration was measured in 35 fish using high-resolution respirometry. It was strongly affected by temperature and showed a drastic drop in OXPHOS respiration fed by complex I and complex I+complex II, while uncoupled respiration plateaued at CTmax temperature. Our results suggest that complex I is an important modulator of the impact of temperature on mitochondrial respiration at high temperatures but is not the main limiting factor in physiological conditions (maximal OXPHOS). Mitochondrial respiration was also affected by fish age, showing a general decrease in older individuals.

Fish hearts expose toxic truth about our cardiovascular health

Fish hearts expose toxic truth about our cardiovascular health Professor Holly Shiels, from the University of Manchester, is the Director of the Company of Biologists and the President of the Fisheries Society of the British Isles. She charts a toxic tide by tracing the path of pollutants from fish hearts to human cardiovascular health. It’s widely known that pollutants damage our oceans. But after researching the effects of an oil spill on the health of fish hearts, Professor Holly Shiels made an alarming discovery - our own hearts are affected in the same way. An explosion at the Deepwater Horizon oil rig off the southern coast of the United States in 2010 unleashed nearly 5 million barrels of oil into the Gulf of Mexico over an excruciating 87 days. This catastrophic event caused one of the most severe ecological disasters in history, devastating the marine environment and obliterating countless forms of life. The scale of environmental devastation was unprecedented, leaving a lasting scar on the region’s fragile habitat.

High temperature and hyperkalemia increase vulnerability of navaga cod (Eleginus nawaga) cardiomyocytes to the ecotoxicant 3-methyl-phenanthrene

Oil and gas mining and transportation in the Arctic can lead to release of polycyclic aromatic hydrocarbons (PAHs) in the ocean and freshwater basins. PAHs are known for their toxic effects in fish hearts, including the inhibition of main ionic currents (IKr, INa and ICaL) in fish cardiac myocytes. The present study is the first one to assess the effect of a particular PAH abundant in crude oil and diesel, namely 3-methyl-phenanthrene (3-MP), on the electrical excitability (EE) of cardiomyocytes from navaga cod (Eleginus nawaga), commercial fish species from the Arctic. Action potentials (APs) were elicited in current-clamp experiments at 9, 15 and 21 °C, and AP characteristics and the current needed to elicit APs were examined. Also, the effects of 3 μM 3-MP were tested at 3 temperatures and in normal (3.5 mM) and high (8 mM) extracellular K+ concentrations.Elevation of temperature leads to hyperpolarization of resting membrane potential and AP shortening, but does not decrease EE. 3-MP was found to suppress EE in cardiomyocytes at 9 and 15 °C, but not at 21 °C. High extracellular K+ itself drastically decreases EE, although it does not worsen the effect of 3-MP. However, combination of hyperthermia and high K+ leads to augmentation of depressive effect of 3-MP on EE. We hypothesize that hyperthermia rescues Na+ channels from inactivation due to membrane hyperpolarization, thereby compensating for the partial inhibition of INa by 3-MP. However, elevation of extracellular K+ nullifies this protective mechanism by depolarizing the resting potential and aggravates the effect of 3-MP.

Use of cardiac cell cultures from salmonids to measure the cardiotoxic effect of environmental pollutants.

Environmental stressors such as micro- and nanosized plastic particles (MNPs) or crude oil have a detrimental effect on aquatic animals; however, the impact upon the cardiovascular system of fish remains relatively under-researched. This study presents a novel approach for investigating the effect of crude oil and MNPs on the cardiac system of fish. We used salmonid larvae and cardiac cell cultures derived from hearts of salmonid fish and exposed them to environmental stressors. Following exposure to plastic particles or crude oil, the larvae exhibited some variation in contraction rate. In contrast, significant alterations in the contraction rate were observed in all cardiac cell cultures. The greatest differences between the control and treatment groups were observed in cardiac cell cultures derived from older brown trout. Following 7 days of exposure to MNPs or crude oil in Atlantic salmon larval hearts or cardiac cell cultures, there were only minor responses noted in mRNA expression of the selected marker genes. These findings show the use of a novel invitro technique contributing to the existing body of knowledge on the impact of MNPs and crude oil on the cardiovascular system of salmonids and the associated risk.

Multiomics analysis reveal the impact of 17α-Ethinylestradiol on mortality in juvenile zebrafish

17α-Ethinylestradiol (EE2) is known for its endocrine-disrupting effects on embryonic and adult fish. However, its impact on juvenile zebrafish has not been well established. In this study, juvenile zebrafish were exposed to EE2 at concentrations of 5 ng/L (low dose, L), 10 ng/L (medium dose, M), and 50 ng/L (high dose, H) from 21 days post-fertilization (dpf) to 49 dpf. We assessed their growth, development, behavior, transcriptome, and metabolome. The findings showed that the survival rate in the EE2-H group was 66.8 %, with all surviving fish displaying stunted growth and swollen, transparent abdomens by 49 dpf. Moreover, severe organ deformities were observed in the gills, kidneys, intestines, and heart of fish in both the EE2-H and EE2-M groups. Co-expression analysis of mRNA and lncRNA revealed that EE2 downregulated the transcription of key genes involved in the cell cycle, DNA replication, and Fanconi anemia signaling pathways. Additionally, metabolomic analysis indicated that EE2 influenced metabolism and development-related signaling pathways. These pathways were also significantly identified based on the genes regulated by lncRNA. Consequently, EE2 induced organ deformities and mortality in juvenile zebrafish by disrupting signaling pathways associated with development and metabolism. The results of this study offer new mechanistic insights into the adverse effects of EE2 on juvenile zebrafish based on multiomics analysis. The juvenile zebrafish are highly sensitive to EE2 exposure, which is not limited to adult and embryonic stages. It is a potential model for studying developmental toxicity.

Highly conductive, stretchable, and biocompatible graphene oxide biocomposite hydrogel for advanced tissue engineering

The importance of hydrogels in tissue engineering cannot be overemphasized due to their resemblance to the native extracellular matrix. However, natural hydrogels with satisfactory biocompatibility exhibit poor mechanical behavior, which hampers their application in stress-bearing soft tissue engineering. Here, we describe the fabrication of a double methacrylated gelatin bioink covalently linked to graphene oxide (GO) via a zero-length crosslinker, digitally light-processed (DLP) printable into 3D complex structures with high fidelity. The resultant natural hydrogel (GelGOMA) exhibits a conductivity of 15.0 S m-1as a result of the delocalization of theπ-orbital from the covalently linked GO. Furthermore, the hydrogel shows a compressive strength of 1.6 MPa, and a 2.0 mm thick GelGOMA can withstand a 1.0 kg ms-1momentum. The printability and mechanical strengths of GelGOMAs were demonstrated by printing a fish heart with a functional fluid pumping mechanism and tricuspid valves. Its biocompatibility, electroconductivity, and physiological relevance enhanced the proliferation and differentiation of myoblasts and neuroblasts and the contraction of human-induced pluripotent stem cell-derived cardiomyocytes. GelGOMA demonstrates the potential for the tissue engineering of functional hearts and wearable electronic devices.

The Functional Significance of Cardiac Looping: Comparative Embryology, Anatomy, and Physiology of the Looped Design of Vertebrate Hearts.

The flow path of vertebrate hearts has a looped configuration characterized by curved (sigmoid) and twisted (chiral) components. The looped heart design is phylogenetically conserved among vertebrates and is thought to represent a significant determinant of cardiac pumping function. It evolves during the embryonic period of development by a process called "cardiac looping". During the past decades, remarkable progress has been made in the uncovering of genetic, molecular, and biophysical factors contributing to cardiac looping. Our present knowledge of the functional consequences of cardiac looping lags behind this impressive progress. This article provides an overview and discussion of the currently available information on looped heart design and its implications for the pumping function. It is emphasized that: (1) looping seems to improve the pumping efficiency of the valveless embryonic heart. (2) bilaterally asymmetric (chiral) looping plays a central role in determining the alignment and separation of the pulmonary and systemic flow paths in the multi-chambered heart of tetrapods. (3) chiral looping is not needed for efficient pumping of the two-chambered hearts of fish. (4) it is the sigmoid curving of the flow path that may improve the pumping efficiency of lower as well as higher vertebrate hearts.

Effect of heat exposure on histology, transcriptomics and co-expression network: A synthetic study in Japanese flounder (Paralichthys olivaceus)

Water temperature has continued to increase as part of global warming. The heart of fish is the center that participates in the physiological limitations of thermal performance. However, only a few studies have focused on the response mechanisms of fish hearts to heat stress. Therefore, the economically important cold-water aquaculture fish, Japanese flounder (Paralichthys olivaceus) was chosen to explore the mechanisms of the heart in response to heat stress. Histological observations indicated that heat stress could widen the sarcoplasmic distance and deepen chromatin staining. Further transcriptome analysis identified 958 differentially expressed genes (DEGs), and significantly enriched “Protein processing in endoplasmic reticulum” pathway and related terms in functional enrichment analysis. Weighted gene co-expression network analysis (WGCNA) showed that different tissues had different response modules and hub genes, and calcium ions (Ca2+) related genes and pathways were noteworthy in the heart specific module. Functional identification of key Ca2+ regulatory hub genes illuminated that caveolin-3 (cav3) was an important gene that participates in controlling the Ca2+ into and out of cells. Meanwhile, overexpression of cav3 could reduce heat stress induced apoptosis. This study could not only be a crucial resource for the response mechanisms underlying heat stress in Japanese flounder, but also provide valuable insights into genetic improvement for heat-resistance.

Cardiac arrhythmias in fish induced by natural and anthropogenic changes in environmental conditions.

A regular heartbeat is essential for maintaining the homeostasis of the vertebrate body. However, environmental pollutants, oxygen deficiency and extreme temperatures can impair heart function in fish. In this Review, we provide an integrative view of the molecular origins of cardiac arrhythmias and their functional consequences, from the level of ion channels to cardiac electrical activity in living fish. First, we describe the current knowledge of the cardiac excitation-contraction coupling of fish, as the electrical activity of the heart and intracellular Ca2+ regulation act as a platform for cardiac arrhythmias. Then, we compile findings on cardiac arrhythmias in fish. Although fish can experience several types of cardiac arrhythmia under stressful conditions, the most typical arrhythmia in fish - both under heat stress and in the presence of toxic substances - is atrioventricular block, which is the inability of the action potential to progress from the atrium to the ventricle. Early and delayed afterdepolarizations are less common in fish hearts than in the hearts of endotherms, perhaps owing to the excitation-contraction coupling properties of the fish heart. In fish hearts, Ca2+-induced Ca2+ release from the sarcoplasmic reticulum plays a smaller role than Ca2+ influx through the sarcolemma. Environmental changes and ion channel toxins can induce arrhythmias in fish and weaken their tolerance to environmental stresses. Although different from endotherm hearts in many respects, fish hearts can serve as a translational model for studying human cardiac arrhythmias, especially for human neonates.

Embryonic Exposure to Organophosphate Flame Retardants (OPFRs) Differentially Induces Cardiotoxicity in Rare Minnow (Gobiocypris rarus).

Organophosphorus flame retardants (OPFRs) such as triphenyl phosphate (TPHP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were reported to impair cardiac function in fish. However, limited information is available regarding their cardiotoxic mechanisms. Using rare minnow (Gobiocypris rarus) as a model, we found that both TPHP and TDCIPP exposures decreased heart rate at 96 h postfertilization (hpf) in embryos. Atropine (an mAChR antagonist) can significantly attenuate the bradycardia caused by TPHP, but only marginally attenuated in TDCIPP treatment, suggesting that TDCIPP-induced bradycardia is independent of mAChR. Unlike TDCIPP, although TPHP-induced bradycardia could be reversed by transferring larvae to a clean medium, the inhibitory effect of AChE activity persisted compared to 96 hpf, indicating the existence of other bradycardia regulatory mechanisms. Transcriptome profiling revealed cardiotoxicity-related pathways in treatments at 24 and 72 hpf in embryos/larvae. Similar transcriptional alterations were also confirmed in the hearts of adult fish. Further studies verified that TPHP and TDCIPP can interfere with Na+/Ca2+ transport and lead to disorders of cardiac excitation-contraction coupling in larvae. Our findings provide useful clues for unveiling the differential cardiotoxic mechanisms of OPFRs and identifying abnormal Na+/Ca2+ transport as one of a select few known factors sufficient to impair fish cardiac function.

Systemic inhibition of mitochondrial fatty acid β-oxidation impedes zebrafish ventricle regeneration

Unlike humans and other mammals, zebrafish demonstrate a remarkable capacity to regenerate their injured hearts throughout life. Mitochondrial fatty acid β-oxidation (FAO) contributes to major energy demands of the adult hearts under physiological conditions; however, its functions in regulating cardiac regeneration and the underlying mechanisms are not completely understood. Different strategies targeting FAO have yield mixed outcomes. Here, we demonstrated that pharmacological inhibition of mitochondrial FAO with mildronate (MD) caused lipid accumulation in zebrafish larvae and suppressed ventricle regeneration. MD treatment impeded cardiogenic factor reactivation and cardiomyocyte (CM) proliferation, and impaired ventricle regeneration could be rescued by exogenous l-carnitine supplementation. Moreover, compared with the ablated hearts of wild-type fish, ventricle regeneration, cardiogenic factor reactivation and CM proliferation were significantly blocked in the ablated hearts of carnitine palmitoyltransferase-1b (cpt1b) knockout zebrafish. Further experiments suggested that NF-κB signaling and increased inflammation may be involved in the impediment of ventricle regeneration caused by systemic mitochondrial FAO inhibition. Overall, our study demonstrates the essential roles of mitochondrial FAO in zebrafish ventricle regeneration and reaffirms the sophisticated and multifaceted roles of FAO in heart regeneration with regard to different injury models and means of FAO inhibition.

From Proliferation to Protection: Immunohistochemical Profiling of Cardiomyocytes and Immune Cells in Molly Fish Hearts

Unlike adult mammalian cardiomyocytes, cardiomyocytes in teleosts display high proliferative capacity throughout adulthood. This study aimed to identify the immunohistochemical profiles of cardiomyocytes and immune cells in the hearts of Molly fish by assessing the immunolabelling expression of key proteins involved in cell proliferation, differentiation, and tissue protection. The cardiac anatomy of Molly fish includes the atrium, ventricle, and bulbus arteriosus. The expression of SOX9, NF-κB, myostatin, and S100 proteins in myocardial cells indicates the proliferative features of the heart in Molly fish. The bulbus arteriosus is characterized by collagenous chambers and smooth muscle cells that express Ach and iba1. The atrium of Molly fish serves as a storage unit for rodlet cells and immune cells. Rodlet cells displayed immunoreactivity to NF-κB, iba1, Olig2, Ach, and S100 proteins, suggesting their roles in the immune response within the heart. Furthermore, telocytes (TCs) have emerged as a significant component of the atrium of Molly fish, expressing Ach, CD68, S100 protein, and iba1. These expressions indicate the involvement of TCs in multiple signaling pathways that contribute to heart architecture. This study delineates the intricate relationship between cardiomyocytes and innate immune cells in Molly fish.

Identification of two miRNAs regulating cardiomyocyte proliferation in an Antarctic icefish

Identification of two miRNAs regulating cardiomyocyte proliferation in an Antarctic icefish

Bromuconazole exposure induces cardiac dysfunction by upregulating the expression LEF1

With the wide application of bromuconazole (BRO), a kind of triazole fungicide, the environmental problems caused by BRO have been paid more and more attention. In this study, adult male zebrafish were exposed to environmental related concentration and the maximum non-lethal concentration for zebrafish larvae (0,50 ng/L and 7.5 mg/L) for 7 days, respectively. Zebrafish exposed to BRO exhibited a significant reduction in body length and an increase in fatness index, indicating adverse physiological changes. Notably, the exposed zebrafish showed enlarged heart ventricular volumes and thinner heart walls. Transcriptome analysis of heart samples showed that BRO exposure mainly affected pathways related to cardiac energy metabolism. In addition, the amount of ATP in the heart tissue was correspondingly reduced, and the expression levels of genes related to controlling ion balance and myosin synthesis in the heart were also altered. The study extended its findings to the rat cardiomyocytes (H9C2), where similar cardiotoxic effects including changes in transcription of genes related to energy metabolism and heart function were also observed, suggesting a potential universal mechanism of BRO-induced cardiotoxicity. In a doxorubicin (DOX) induced larval zebrafish heart failure model, the expression of lymphoid enhancer-binding factor 1(LEF1), a key gene in the Wnt/β-catenin signaling pathway, was significantly increased in larval zebrafish and adult fish heart tissues and cardiomyocytes, suggesting that LEF1 might play an important role in BRO-induced cardiotoxicity. Taken together, BRO exposure could interfere with cardiac function and metabolic capacity by abnormal activation the expression of LEF1. The study emphasized the urgent need for monitoring and regulating BRO due to its harmful effects on the hearts of aquatic organisms.

3-Methyl-phenanthrene (3-MP) disrupts the electrical and contractile activity of the heart of the polar fish, navaga cod (Eleginus nawaga)

Alkylated polycyclic aromatic hydrocarbons are abundant in crude oil and are enriched during petroleum refinement but knowledge of their cardiotoxicity remains limited. Polycyclic aromatic hydrocarbons (PAHs) are considered the main hazardous components in crude oil and the tricyclic PAH phenanthrene has been singled out for its direct effects on cardiac tissue in mammals and fish. Here we test the impact of the monomethylated phenanthrene, 3-methylphenanthrene (3-MP), on the contractile and electrical function of the atrium and ventricle of a polar fish, the navaga cod (Eleginus nawaga). Using patch-clamp electrophysiology in atrial and ventricular cardiomyocytes we show that 3-MP is a potent inhibitor of the delayed rectifier current IKr (IC50 = 0.25 μM) and prolongs ventricular action potential duration. Unlike the parent compound phenanthrene, 3-MP did not reduce the amplitude of the L-type Ca2+ current (ICa) but it accelerated current inactivation thus reducing charge transfer across the myocyte membrane and compromising pressure development of the whole heart. 3-MP was a potent inhibitor (IC50 = 4.7 μM) of the sodium current (INa), slowing the upstroke of the action potential in isolated cells, slowing conduction velocity across the atrium measured with optical mapping, and increasing atrio-ventricular delay in a working whole heart preparation. Together, these findings reveal the strong cardiotoxic potential of this phenanthrene derivative on the fish heart. As 3-MP and other alkylated phenanthrenes comprise a large fraction of the PAHs in crude oil mixtures, these findings are worrisome for Arctic species facing increasing incidence of spills and leaks from the petroleum industry. 3-MP is also a major component of polluted air but is not routinely measured. This is also of concern if the hearts of humans and other terrestrial animals respond to this PAH in a similar manner to fish.