Acclimation of Hairless Spontaneously Hypertensive Rat to Ambient Temperature Attenuates Hypertension-Induced Pro-Arrhythmic Downregulation of Cx43 in the Left Heart Ventricle of Males
Objectives: Due to poor treatment adherence and lifestyle-based interventions, chronic hypertension is a dominant risk factor predisposing individuals to heart failure and malignant arrhythmias. We investigated the impact of the postnatal acclimation of hairless SHR to ambient temperature that is, f...
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2024-11-01
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| author | Katarina Andelova Matus Sykora Veronika Farkasova Tatiana Stankovicova Barbara Szeiffova Bacova Vladimir Knezl Tamara Egan Benova Michal Pravenec Narcis Tribulova |
| author_facet | Katarina Andelova Matus Sykora Veronika Farkasova Tatiana Stankovicova Barbara Szeiffova Bacova Vladimir Knezl Tamara Egan Benova Michal Pravenec Narcis Tribulova |
| author_sort | Katarina Andelova |
| collection | DOAJ |
| description | Objectives: Due to poor treatment adherence and lifestyle-based interventions, chronic hypertension is a dominant risk factor predisposing individuals to heart failure and malignant arrhythmias. We investigated the impact of the postnatal acclimation of hairless SHR to ambient temperature that is, for them, below thermoneutrality, on the electrical coupling protein connexin-43 (Cx43) and pro-fibrotic markers in both heart ventricles of male and female hairless SHR rats compared to the wild SHR. Methods: Some 6-month-acclimated male and female hairless SHR as well as age- and sex-matched wild SHR were included and compared with the non-hypertensive Wistar strain. The left and right heart ventricles were examined for Cx43 topology, myocardial structure, and the histochemistry of capillaries. The protein levels of Cx43, relevant protein kinases, and extracellular matrix proteins (ECMs) were determined by immunoblotting. MMP-2 activity was assessed via zymography, and susceptibility to malignant arrhythmias was tested ex vivo. Results: Cx43 and its phosphorylated variant pCx43<sup>368</sup> were significantly reduced in the left heart ventricles of wild SHR males, while to a lesser extent in the hairless SHR. In contrast, these proteins were not significantly altered in the right heart ventricles of males or in both heart ventricles in females, regardless of the rat strain. Pro-arrhythmic Cx43 topology was detected in the left heart ventricle of wild SHR and to a lesser extent in hairless SHR males. TGFβ protein was significantly increased only in the left ventricle of the wild SHR males. MMP-2 activity was increased in the right ventricle but not in the left ventricles of both males and females, regardless of the rat strain. Conclusions: The findings indicate that the postnatal acclimation of hairless SHR to ambient temperature hampers the downregulation of Cx43 in the left heart ventricle compared to wild SHR males. The decline of Cx43 was much less pronounced in females and not observed in the right heart ventricles, regardless of the rat strain. It may impact the susceptibility of the heart to malignant arrhythmias. |
| format | Article |
| id | doaj-art-7dc35c6e32f94cd5b10dc03c1642e144 |
| institution | DOAJ |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-7dc35c6e32f94cd5b10dc03c1642e1442025-08-20T02:53:31ZengMDPI AGBiomolecules2218-273X2024-11-011412150910.3390/biom14121509Acclimation of Hairless Spontaneously Hypertensive Rat to Ambient Temperature Attenuates Hypertension-Induced Pro-Arrhythmic Downregulation of Cx43 in the Left Heart Ventricle of MalesKatarina Andelova0Matus Sykora1Veronika Farkasova2Tatiana Stankovicova3Barbara Szeiffova Bacova4Vladimir Knezl5Tamara Egan Benova6Michal Pravenec7Narcis Tribulova8Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, SlovakiaCentre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, SlovakiaCentre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, SlovakiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, 832 32 Bratislava, SlovakiaCentre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, SlovakiaCentre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, SlovakiaCentre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, SlovakiaInstitute of Physiology, v.v.i., Academy of Sciences of the Czech Republic, 14220 Prague, Czech RepublicCentre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, SlovakiaObjectives: Due to poor treatment adherence and lifestyle-based interventions, chronic hypertension is a dominant risk factor predisposing individuals to heart failure and malignant arrhythmias. We investigated the impact of the postnatal acclimation of hairless SHR to ambient temperature that is, for them, below thermoneutrality, on the electrical coupling protein connexin-43 (Cx43) and pro-fibrotic markers in both heart ventricles of male and female hairless SHR rats compared to the wild SHR. Methods: Some 6-month-acclimated male and female hairless SHR as well as age- and sex-matched wild SHR were included and compared with the non-hypertensive Wistar strain. The left and right heart ventricles were examined for Cx43 topology, myocardial structure, and the histochemistry of capillaries. The protein levels of Cx43, relevant protein kinases, and extracellular matrix proteins (ECMs) were determined by immunoblotting. MMP-2 activity was assessed via zymography, and susceptibility to malignant arrhythmias was tested ex vivo. Results: Cx43 and its phosphorylated variant pCx43<sup>368</sup> were significantly reduced in the left heart ventricles of wild SHR males, while to a lesser extent in the hairless SHR. In contrast, these proteins were not significantly altered in the right heart ventricles of males or in both heart ventricles in females, regardless of the rat strain. Pro-arrhythmic Cx43 topology was detected in the left heart ventricle of wild SHR and to a lesser extent in hairless SHR males. TGFβ protein was significantly increased only in the left ventricle of the wild SHR males. MMP-2 activity was increased in the right ventricle but not in the left ventricles of both males and females, regardless of the rat strain. Conclusions: The findings indicate that the postnatal acclimation of hairless SHR to ambient temperature hampers the downregulation of Cx43 in the left heart ventricle compared to wild SHR males. The decline of Cx43 was much less pronounced in females and not observed in the right heart ventricles, regardless of the rat strain. It may impact the susceptibility of the heart to malignant arrhythmias.https://www.mdpi.com/2218-273X/14/12/1509hairless SHRmalesfemalesleft and right heart ventricleconnexin43arrhythmias |
| spellingShingle | Katarina Andelova Matus Sykora Veronika Farkasova Tatiana Stankovicova Barbara Szeiffova Bacova Vladimir Knezl Tamara Egan Benova Michal Pravenec Narcis Tribulova Acclimation of Hairless Spontaneously Hypertensive Rat to Ambient Temperature Attenuates Hypertension-Induced Pro-Arrhythmic Downregulation of Cx43 in the Left Heart Ventricle of Males Biomolecules hairless SHR males females left and right heart ventricle connexin43 arrhythmias |
| title | Acclimation of Hairless Spontaneously Hypertensive Rat to Ambient Temperature Attenuates Hypertension-Induced Pro-Arrhythmic Downregulation of Cx43 in the Left Heart Ventricle of Males |
| title_full | Acclimation of Hairless Spontaneously Hypertensive Rat to Ambient Temperature Attenuates Hypertension-Induced Pro-Arrhythmic Downregulation of Cx43 in the Left Heart Ventricle of Males |
| title_fullStr | Acclimation of Hairless Spontaneously Hypertensive Rat to Ambient Temperature Attenuates Hypertension-Induced Pro-Arrhythmic Downregulation of Cx43 in the Left Heart Ventricle of Males |
| title_full_unstemmed | Acclimation of Hairless Spontaneously Hypertensive Rat to Ambient Temperature Attenuates Hypertension-Induced Pro-Arrhythmic Downregulation of Cx43 in the Left Heart Ventricle of Males |
| title_short | Acclimation of Hairless Spontaneously Hypertensive Rat to Ambient Temperature Attenuates Hypertension-Induced Pro-Arrhythmic Downregulation of Cx43 in the Left Heart Ventricle of Males |
| title_sort | acclimation of hairless spontaneously hypertensive rat to ambient temperature attenuates hypertension induced pro arrhythmic downregulation of cx43 in the left heart ventricle of males |
| topic | hairless SHR males females left and right heart ventricle connexin43 arrhythmias |
| url | https://www.mdpi.com/2218-273X/14/12/1509 |
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