The Dynamic Nature of Hypertrophic and Fibrotic Remodeling of the Fish Ventricle

Abstract

Chronic pressure or volume overload can cause the vertebrate heart to remodel. The hearts of fish remodel in response to seasonal temperature change. Here we focus on the passive properties of the fish heart. Building upon our previous work on thermal-remodeling of the rainbow trout ventricle, we hypothesized that chronic cooling would initiate fibrotic cardiac remodeling, with increased myocardial stiffness, similar to that seen with pathological hypertrophy in mammals. We hypothesized that, in contrast to pathological hypertrophy in mammals, the remodeling response in fish would be plastic and the opposite response would occur following chronic warming. Rainbow trout held at 10°C (control group) were chronically (>8 weeks) exposed to cooling (5°C) or warming (18°C). Chronic cold induced hypertrophy in the highly trabeculated inner layer of the fish heart, with a 41% increase in myocyte bundle cross-sectional area, and an up-regulation of hypertrophic marker genes. Cold acclimation also increased collagen deposition by 1.7-fold and caused an up-regulation of collagen promoting genes. In contrast, chronic warming reduced myocyte bundle cross-sectional area, expression of hypertrophic markers and collagen deposition. Functionally, the cold-induced fibrosis and hypertrophy were associated with increased passive stiffness of the whole ventricle and with increased micromechanical stiffness of tissue sections. The opposite occurred with chronic warming. These findings suggest chronic cooling in the trout heart invokes a hypertrophic phenotype with increased cardiac stiffness and fibrosis that are associated with pathological hypertrophy in the mammalian heart. The loss of collagen and increased compliance following warming is particularly interesting as it suggests fibrosis may oscillate seasonally in the fish heart, revealing a more dynamic nature than the fibrosis associated with dysfunction in mammals.

Thermal acclimation and seasonal acclimatization: a comparative study of cardiac response to prolonged temperature change in shorthorn sculpin

“…However, we did not measure contractile strength of the sculpin heart, so we can only speculate that the larger I Ca in winter-acclimatized fish would have improved force production compared with the cold-acclimated group. Indeed, the cellular hypertrophy we observed following winter acclimatization would support the idea of morphological remodelling to increase cardiac contractile force in the cold Vornanen, 1998, 1999;Keen et al, 2016;Klaiman et al, 2011;Vornanen et al, 2005). SR Ca 2+ cycling may also contribute to cellular Ca 2+ flux in this species and although we did not measure SR function in this study, other studies with fish show cold acclimation increases SR complement and SR function [i.e.…”

“…Indeed, Johansen et al (2011Johansen et al ( , 2017 found profound and pathological hypertrophic and fibrotic remodelling in salmonid hearts in response to artificially elevated cortisol levels. Moreover, a large number of studies demonstrated myocyte hypertrophy in fishes following cold acclimation (Aho and Vornanen, 1998;Driedzic et al, 1996;Farrell et al, 1988;Keen et al, 2016Keen et al, , 2018Kent et al, 1988;Klaiman et al, 2011;Vornanen et al, 2005) where the influence of hormones may be less. In these studies, the hypertrophy has been attributed to the increased haemodynamic load on the heart caused by increased blood viscosity in the cold.…”

LTBP2 knockdown by siRNA reverses myocardial oxidative stress injury, fibrosis and remodelling during dilated cardiomyopathy

“…Col‐I and Col‐III are essential components of the cardiac extracellular matrix (ECM) maintaining the functional integrity of the heart . Differential increases of Col‐I and Col‐III lead to an increased Col‐I/Col‐III ratio in DCM myocardium, with Col‐I providing substantial tensile strength and stiffness, which contributes to systolic and particularly diastolic dysfunction in DCM . The activation of NF‐κB in the heart is also limited by the type and intensity of the stimulus and the interactions with a variety of protein complexes .…”

“…33 Differential increases of Col-I and Col-III lead to an increased Col-I/Col-III ratio in DCM myocardium, with Col-I providing substantial tensile strength and stiffness, which contributes to systolic and particularly diastolic dysfunction in DCM. 34 The activation of NF-κB in the heart is also limited by the type and intensity of the stimulus and the interactions with a variety of protein complexes. 16 In this way, NF-κB is involved in many cardiac processes, including development, contraction, atherosclerosis, inflammation, ischaemia, hypertrophy, angina, dilation and heart failure.…”

Effects of temperature on juvenile Dungeness crab,Metacarcinus magister(Dana): survival, moulting, and mTOR signalling and neuropeptide gene expression in eyestalk ganglia, moulting gland (Y-organ), and heart

“…Phenotypic changes of the heart are mirrored in changes in mRNA expression of genes involved in muscle growth both during warm and cold acclimation in fish (e.g. Keen et al, 2016). Furthermore, cardiac transcriptomes vary after heat shock according to seasonal and latitudinal acclimatization in porcelain crabs (Stillman and Tagmount, 2009).…”