Heat acclimation mediated cardioprotection is controlled by mitochondrial metabolic remodeling involving HIF-1α

Mreisat, Ahmad; Kanaani, H.; Saada, Ann; Horowitz, Michal

doi:10.1016/j.jtherbio.2020.102691

Cited by 9 publications

(5 citation statements)

References 47 publications

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“…The inhibitory effect of lactate decreased respiration with either palmitoyl-carnitine (37%) or pyruvate (20%) (Huynh and Pamenter, 2022). On the other hand, heat acclimation has been found to increase the expression of mitochondrial LDH (LDHB; the isoform associated with the oxidation of lactate to pyruvate) in rat heart (Mreisat et al, 2020), which should, paradoxically, lead to increased pyruvate oxidation. In isolated rat brain mitochondria, L-lactate has been observed to partially inhibit (29%) mitochondrial respiration with pyruvate (Ling et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Lactate shuttling as an allostatic means of thermoregulation in the brain

Kane,

Foo,

Noftall

et al. 2023

Front. Neurosci.

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Lactate, the redox-balanced end product of glycolysis, travels within and between cells to fulfill an array of physiologic functions. While evidence for the centrality of this lactate shuttling in mammalian metabolism continues to mount, its application to physical bioenergetics remains underexplored. Lactate represents a metabolic “cul-de-sac,” as it can only re-enter metabolism by first being converted back to pyruvate by lactate dehydrogenase (LDH). Given the differential distribution of lactate producing/consuming tissues during metabolic stresses (e.g., exercise), we hypothesize that lactate shuttling vis-à-vis the exchange of extracellular lactate between tissues serves a thermoregulatory function, i.e., an allostatic strategy to mitigate the consequences of elevated metabolic heat. To explore this idea, the rates of heat and respiratory oxygen consumption in saponin-permeabilized rat cortical brain samples fed lactate or pyruvate were measured. Heat and respiratory oxygen consumption rates, and calorespirometric ratios were lower during lactate vs. pyruvate-linked respiration. These results support the hypothesis of allostatic thermoregulation in the brain with lactate.

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Section: Discussionmentioning

confidence: 99%

Lactate shuttling as an allostatic means of thermoregulation in the brain

Kane,

Foo,

Noftall

et al. 2023

Front. Neurosci.

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“…However, this number is too high for animal experiments. According to the principle of reduction in the Replacement, Reduction and Refinement Principle (3Rs) of animal experiments and with reference to previous studies [35][36][37], we ultimately divided 10 rats into groups; the temperature data of 5 rats in each group were published, and the expression levels of heat shock proteins in various organs after the completion of heat acclimation training were also published [33]. Unpublished data on rat body temperature and body weight are presented here.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Proteomics Provided Insights into the Protective Effects of Heat Acclimation on the Rat Hypothalamus after Exertional Heatstroke

Xv,

Ma,

et al. 2024

J. Integr. Neurosci.

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Background: The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study aimed to address these questions. Methods: In the present study, rats were randomly assigned to the control, EHS, HA, or HA + EHS groups (n = 9). Hematoxylin and eosin (H&E) staining was used to examine pathology. Tandem mass tag (TMT)-based proteomic analysis was utilized to explore the impact of HA on the protein expression profile of the hypothalamus after EHS. Bioinformatics analysis was used to predict the functions of the differentially expressed proteins. The differential proteins were validated by western blotting. An enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines in the serum. Results: The H&E staining (n = 5) results revealed that there were less structural changes in hypothalamus in the HA + EHS group compared with the EHS group. Proteomic analysis (n = 4) revealed that proinflammatory proteins such as argininosuccinate synthetase (ASS1), high mobility group protein B2 (HMGB2) and vimentin were evidently downregulated in the HA + EHS group. The levels of interleukin (IL)-1β, IL-1, and IL-8 were decreased in the serum samples (n = 3) from HA + EHS rats. Conclusions: HA may alleviate hypothalamic damage caused by heat attack by inhibiting inflammatory activities, and ASS1, HMGB2 and vimentin could be candidate factors involved in the exact mechanism.

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“…The review by Budde et al (2022) , on HFPEF supports our theories and emphasizes that ROS and Ca 2+ sensitivity are comorbid factors in HFPEF. The hazards of both ROS and alterations in Ca 2+ sensitivity decrease upon LTHA ( Mreisat et al, 2020 ). Based on the beneficial effects of LTHA on cardiac and vascular compliance described in the present review, it seems that patients with HFPEF could benefit from heat acclimation, such as from its epigenetic impacts, (e.g., Titin N2B/N2BA (stiff/complaint isoforms) ratio ( Li et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the shift from the fast to slow myosin phenotype, LTHA increases endurance during Ca 2+ overload ( Mirit et al, 2000 ) and changes the Ca 2+ transient/amplitude systolic motion ratio ( Kodesh et al, 2011 ). Furthermore ( Horowitz et al, 2004 ; Mreisat et al, 2020 ), LTHA is also limits the negative impacts of reactive oxygen species (ROS). These physiological markers support our hypothesis that titin and its interconnection with the ECM contribute to the adaptive signaling in the passive and trained LTHA hearts ( Kodesh et al, 2011 ).…”

Section: Human Translational Studies On Left Ventricular Compliance A...mentioning

confidence: 99%

Vascular compliance and left ventricular compliance cross talk: Implications for using long-term heat acclimation in cardiac care

Horowitz

Hasin²

2023

Front. Physiol.

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1) The first evidence of the beneficial impact of Long-Term-Heat-Acclimation (LTHA) on cardio-vascular compliance was the positive inotropic response and improved left ventricular (LV) compliance noted when isolated hearts from LTHA rats were studied. Human echo study demonstrates that passive HA affects the right ventricle and the atria as well. 2) There is a cross-talk between vascular and cardiac compliance. Vascular compliance per se is defined by central venous pressure—Blood volume relationship—Global Vascular Compliance (GVC). It is determined by the sum of the vascular compliance of the vessels in every organ in any physiological state, varies with LTHA and thus influences cardiac performance. LTHA improves endothelial function, increases NO (nitric oxide) production, in-turn stimulating alterations in ECM (extracellular matrix) via the TGF β1-SMAD pathway. 3) LTHA is associated with transformation from fast to slow myosin, heat acclimation ischemic/hypoxic cross-tolerance and alterations in the extracellular matrix. 4) A human translational study demonstrated improved LV compliance following bypass surgery in LTHA subjects compared to controls. 5) Diastolic dysfunction and the impact of comorbidities with vascular and non- vascular origins are major contributors to the syndrome of heart failure with preserved ejection function (HFPEF). Unfortunately, there is a paucity of treatment modalities that improve diastolic dysfunction. 6) In the current mini-review we suggest that LTHA may be beneficial to HFPEF patients by remodeling cardiac compliance and vascular response.

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Heat acclimation mediated cardioprotection is controlled by mitochondrial metabolic remodeling involving HIF-1α

Cited by 9 publications

References 47 publications

Lactate shuttling as an allostatic means of thermoregulation in the brain

Lactate shuttling as an allostatic means of thermoregulation in the brain

Quantitative Proteomics Provided Insights into the Protective Effects of Heat Acclimation on the Rat Hypothalamus after Exertional Heatstroke

Vascular compliance and left ventricular compliance cross talk: Implications for using long-term heat acclimation in cardiac care

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