Influence of carvedilol and thyroid hormones on inflammatory proteins and cardioprotective factor HIF-1α in the infarcted heart

• Published in: Canadian journal of physiology and pharmacology Vol. 101; no. 2; pp. 106 - 116
• Main Authors: Ortiz, Vanessa Duarte, Teixeira, Rayane Brinck, Türck, Patrick, Corssac, Giana Blume, Belló-Klein, Adriane, de Castro, Alexandre Luz, Araujo, Alex Sander da Rosa
• Format: Journal Article
• Language: English
• Published: Canada Canadian Science Publishing NRC Research Press 01.02.2023
• Subjects: Animals; Blood pressure; Carvedilol - pharmacology; Carvedilol - therapeutic use; Heart; Hemodynamics; Hypoxia-inducible factor 1a; Inflammasomes; Inflammation; Male; Muscle contraction; MyD88 protein; Myeloid Differentiation Factor 88 - metabolism; Myocardial infarction; Myocardial Infarction - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Rats; Rats, Wistar; Thyroid gland; Thyroid Hormones; TLR4 protein; Toll-like receptors; Ventricle; TLR4 pathway; HIF-1α; NLRP3 inflammasome; beta blocker; thyroid hormones
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2022-0355

Inflammatory pathways of Toll-like receptor 4 (TLR4) and NLRP3 inflammasome contribute to acute myocardial infarction (AMI) pathophysiology. The hypoxia-inducible factor 1α (HIF-1α), however, is a key transcription factor related to cardioprotection. This study aimed to compare the influence of carvedilol and thyroid hormones (TH) on inflammatory and HIF-1α proteins and on cardiac haemodynamics in the infarcted heart. Male Wistar rats were allocated into five groups: sham-operated group (SHAM), infarcted group (MI), infarcted treated with the carvedilol group (MI + C), infarcted treated with the TH group (MI + TH), and infarcted co-treated with the carvedilol and TH group (MI + C + TH). Haemodynamic analysis was assessed 15 days post-AMI. The left ventricle (LV) was collected for morphometric and Western blot analysis. The MI group presented LV systolic pressure reduction, LV end-diastolic pressure elevation, and contractility index decrease compared to the SHAM group. The MI + C, MI + TH, and MI + C + TH groups did not reveal such alterations compared to the SHAM group. The MI + TH and MI + C + TH groups presented reduced MyD88 and NLRP3 and increased HIF-1α levels. In conclusion, all treatments preserve the cardiac haemodynamic, and only TH, as isolated treatment or in co-treatment with carvedilol, was able to reduce MyD88 and NLRP3 and increase HIF-1α in the infarcted heart.