Gradual cold acclimation induces cardioprotection without affecting adrenergic β-receptor-mediated adenylyl cyclase signaling

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F20%3A10413518" target="_blank" >RIV/00216208:11310/20:10413518 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SEx_YpqKvY" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SEx_YpqKvY</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1152/japplphysiol.00511.2019" target="_blank" >10.1152/japplphysiol.00511.2019</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Gradual cold acclimation induces cardioprotection without affecting adrenergic β-receptor-mediated adenylyl cyclase signaling

Popis výsledku v původním jazyce

Novel strategies are needed that can stimulate endogenous signaling pathways to protect the heart from myocardial infarction. The present study tested the hypothesis that appropriate regimen of cold acclimation (CA) may provide a promising approach for improving myocardial resistance to ischemia/reperfusion (UR) injury without negative side effects. We evaluated myocardial UR injury, mitochondrial swelling, and beta-adrenergic receptor (β-AR)-adenylyl cyclase-mediated signaling. Male Wistar rats were exposed to CA (8 °C, 8 h/day for a week, followed by 4 wk at 8 °C for 24 h/day), while the recovery group (CAR) was kept at 24 °C for an additional 2 wk. The myocardial infarction induced by coronary occlusion for 20 min followed by 3-h reperfusion was reduced from 56% in controls to 30% and 23% after CA and CAR. respectively. In line, the rate of mitochondrial swelling at 200 μM Ca(2+) was decreased in both groups. Acute administration of metoprolol decreased infarction in control group and did not affect the CA-elicited cardiprotection. Accordingly, neither β1-AR-G(s)α-adenyly-1- cyclase signaling. stimulated with specific ligands, nor p-PKA/PICA ratios were affected after CA or CAR. Importantly. Western blot and immunofluorescence analyses revealed β2- and β3-AR protein enrichment in membranes in both experimental groups. We conclude that gradual cold acclimation results in a persisting increase of myocardial resistance to I/R injury without hypertension and hypertrophy. The cardioprotective phenotype is associated with unaltered adenylyl cyclase signaling and increased mitochondrial resistance to Ca2+-overload. The potential role of upregulated β2/β3-AR pathways remains to be elucidated.NEW &amp; NOTEWORTHY: We present a new model of mild gradual cold acclimation increasing tolerance to myocardial ischemia/reperfusion injury without hypertension and hypertrophy. Cardioprotective phenotype is accompanied by unaltered adenylyl cyclase signaling and increased mitochondrial resistance to Ca(2+)-overload. The potential role of upregulated β2/β3-adrenoreceptor activation is considered. These findings may stimulate the development of novel preventive and therapeutic strategies against myocardial ischemia/reperfusion injury.

Název v anglickém jazyce

Gradual cold acclimation induces cardioprotection without affecting adrenergic β-receptor-mediated adenylyl cyclase signaling

Popis výsledku anglicky

Novel strategies are needed that can stimulate endogenous signaling pathways to protect the heart from myocardial infarction. The present study tested the hypothesis that appropriate regimen of cold acclimation (CA) may provide a promising approach for improving myocardial resistance to ischemia/reperfusion (UR) injury without negative side effects. We evaluated myocardial UR injury, mitochondrial swelling, and beta-adrenergic receptor (β-AR)-adenylyl cyclase-mediated signaling. Male Wistar rats were exposed to CA (8 °C, 8 h/day for a week, followed by 4 wk at 8 °C for 24 h/day), while the recovery group (CAR) was kept at 24 °C for an additional 2 wk. The myocardial infarction induced by coronary occlusion for 20 min followed by 3-h reperfusion was reduced from 56% in controls to 30% and 23% after CA and CAR. respectively. In line, the rate of mitochondrial swelling at 200 μM Ca(2+) was decreased in both groups. Acute administration of metoprolol decreased infarction in control group and did not affect the CA-elicited cardiprotection. Accordingly, neither β1-AR-G(s)α-adenyly-1- cyclase signaling. stimulated with specific ligands, nor p-PKA/PICA ratios were affected after CA or CAR. Importantly. Western blot and immunofluorescence analyses revealed β2- and β3-AR protein enrichment in membranes in both experimental groups. We conclude that gradual cold acclimation results in a persisting increase of myocardial resistance to I/R injury without hypertension and hypertrophy. The cardioprotective phenotype is associated with unaltered adenylyl cyclase signaling and increased mitochondrial resistance to Ca2+-overload. The potential role of upregulated β2/β3-AR pathways remains to be elucidated.NEW &amp; NOTEWORTHY: We present a new model of mild gradual cold acclimation increasing tolerance to myocardial ischemia/reperfusion injury without hypertension and hypertrophy. Cardioprotective phenotype is accompanied by unaltered adenylyl cyclase signaling and increased mitochondrial resistance to Ca(2+)-overload. The potential role of upregulated β2/β3-adrenoreceptor activation is considered. These findings may stimulate the development of novel preventive and therapeutic strategies against myocardial ischemia/reperfusion injury.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

<a href="/cs/project/GA17-07748S" target="_blank" >GA17-07748S: Kardioprotektivní potenciál chladové adaptace u potkanů: úloha odpřahujících proteinů.</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Applied Physiology

ISSN

8750-7587

e-ISSN

1522-1601

Svazek periodika

128

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

1023-1032

Kód UT WoS článku

000528322200031

EID výsledku v databázi Scopus

2-s2.0-85083545249