Your browser doesn't support javascript.
loading
Antifibrotic effect of the P2X7 receptor antagonist A740003 against acute myocardial infarction-induced fibrotic remodelling.
Almusallam, Noura; Alonazi, Asma; Dayel, Anfal Bin; Almubarak, Abdullah; Ali, Rizwan; Althakfi, Wajd; Ali, Rehab; Alrasheed, Nouf.
Afiliación
  • Almusallam N; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • Alonazi A; Pharmaceutical Care Department, King Saud Medical City, Ministry of Health, Riyadh 11196, Saudi Arabia.
  • Dayel AB; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • Almubarak A; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • Ali R; Experimental Surgery and Animal Laboratory, Prince Naif Bin Abdul Aziz Health Research Center, King Saud University, Riyadh 11451, Saudi Arabia.
  • Althakfi W; King Abdullah International Medical Research Center, Medical Research Core Facility and Platforms, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh 11481, Saudi Arabia.
  • Ali R; Department of Pathology, College of Medicine, KSUMC, King Saud University, Riyadh 11451, Saudi Arabia.
  • Alrasheed N; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Saudi Pharm J ; 32(7): 102102, 2024 Jul.
Article en En | MEDLINE | ID: mdl-39035363
ABSTRACT
Post-acute myocardial infarction (AMI) fibrosis is a pathophysiologic process characterised by activation of the profibrotic mediator, transforming growth factor-ß (TGF-ß). AMI is associated with a substantial increase in the levels of extracellular adenosine triphosphate (eATP), which acts on the purinergic P2X7-receptor (P2X7-R) and triggers an inflammatory response that contributes to myocardial fibrotic remodelling. P2X7-R has been implicated in several cardiovascular diseases; however, its role in the regulation of cardiac fibrosis remains unclear. Therefore, the current study aimed to determine the effect of the P2X7-R antagonist, A740003, on post-AMI fibrosis, via the profibrotic TGF-ß1/Smad signalling pathway, and elucidate whether its effect is mediated via the modulation of GSK-3ß. AMI was induced by surgical ligation of the left anterior descending coronary artery, Thereafter, animals were divided into groups sham control, MI-untreated, MI-vehicle, and MI-A740003 (50 mg/kg/day) and treated for seven days accordingly. The heart weight/body weight ratio of untreated-ligated rats significantly increased by 15.1 %, creatine kinase-MB (CK-MB) significantly increased by 40 %, troponin-I levels significantly increased by 25.4 %, and lactate dehydrogenase significantly increased by 47.2 %, indicating myocardial damage confirmed by morphological changes and massive cardiac fibrosis. The protein expression of cardiac fibronectin, TGF-ß1, and p-Smad2 were also upregulated by 143 %, 40 %, and 8 %, respectively, indicating cardiac fibrosis. The treatment of ligated rats with A740003 led to improvement in all the above-mentioned parameters. Overall, A740003 exhibits potential cardio-protective effects on post-AMI fibrotic remodelling in the animal model of AMI through P2X7-R blockade, possibly by downregulating the profibrotic TGF-ß1/Smad signalling pathway and restoring GSK-3ß phosphorylation. Altogether, treatment with A740003 could serve as a new cardioprotective strategy to attenuate post-AMI fibrotic remodelling.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Saudi Pharm J Año: 2024 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación:
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Saudi Pharm J Año: 2024 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: