Refaat A Eid1, Mahmoud A Alkhateeb2, Mubarak Al-Shraim1, Samy M Eleawa3, Abdullah S Shatoor4, Attalla Farag El-Kott5, Mohamed Samir Ahmed Zaki6, Khalid A Shatoor7, Ismaeel Bin-Jaliah8, Fahaid H Al-Hashem8. 1. a Department of Pathology, College of Medicine , King Khalid University , Abha , Saudi Arabia. 2. b Department of Basic Medical Sciences, College of Medicine , King Saud bin Abdulaziz University for Health Sciences , Riyadh , Saudi Arabia. 3. c Department of Applied Medical Sciences, College of Health Sciences , PAAET , Kuwait. 4. d Cardiology section, Department of Medicine, College of Medicine , King Khalid University , Abha , Saudi Arabia. 5. e Department of Biology, College of Science , King Khalid University , Abha , Saudi Arabia. 6. f Department of Anatomy, College of Medicine , King Khalid University , Abha , Saudi Arabia. 7. g College of Medicine , King Khalid University , Abha , Saudi Arabia. 8. h Department of Physiology, College of Medicine , King Khalid University , Abha , Saudi Arabia.
Abstract
CONTEXT: Mechanisms by which ghrelin affords its cardioprotection in mammals remained unclear. OBJECTIVE: To examine if ghrelin confers cardio-protection during cardiac remodelling post-MI by modulating the RAF-1-MEK1/2-ERK1/2 signalling pathway. MATERIALS AND METHODS: Rats were divided into control, sham, sham + ghrelin, myocardial infarction (MI), and MI + ghrelin groups. Ghrelin (100 µg/kg) was administered for 21 days, starting one-day post-MI. RESULTS: Ghrelin enhanced cardiac contractility and the activities of antioxidant enzymes, lowered serum levels of enzyme markers of cardiac dysfunction, and lowered inflammatory mediator levels. Ghrelin increased levels of phospho-Raf-1 (Ser338), phospho-MEK1/2 (Ser217/221), phospho-ERK1/2 (Thr202/Tyr204), and of their downstream target p-BAD (Ser112) and inhibited the cleavage of caspase-3. Concomitantly, ghrelin prevented the increases in the levels of fibrotic markers, including α-smooth muscle actin (α-SMA), metalloproteinase-9 (MPP-9), and type III collagen. CONCLUSION: Post-MI in rats, ghrelin stimulated Raf-1-MEK1/2-ERK1/2-BAD signalling in the LV infarct areas, accounting for its anti-apoptotic effect, enhancing cardiac function, and inhibiting cardiac fibrosis during cardiac remodelling.
CONTEXT: Mechanisms by which ghrelin affords its cardioprotection in mammals remained unclear. OBJECTIVE: To examine if ghrelin confers cardio-protection during cardiac remodelling post-MI by modulating the RAF-1-MEK1/2-ERK1/2 signalling pathway. MATERIALS AND METHODS:Rats were divided into control, sham, sham + ghrelin, myocardial infarction (MI), and MI + ghrelin groups. Ghrelin (100 µg/kg) was administered for 21 days, starting one-day post-MI. RESULTS:Ghrelin enhanced cardiac contractility and the activities of antioxidant enzymes, lowered serum levels of enzyme markers of cardiac dysfunction, and lowered inflammatory mediator levels. Ghrelin increased levels of phospho-Raf-1 (Ser338), phospho-MEK1/2 (Ser217/221), phospho-ERK1/2 (Thr202/Tyr204), and of their downstream target p-BAD (Ser112) and inhibited the cleavage of caspase-3. Concomitantly, ghrelin prevented the increases in the levels of fibrotic markers, including α-smooth muscle actin (α-SMA), metalloproteinase-9 (MPP-9), and type III collagen. CONCLUSION: Post-MI in rats, ghrelin stimulated Raf-1-MEK1/2-ERK1/2-BAD signalling in the LV infarct areas, accounting for its anti-apoptotic effect, enhancing cardiac function, and inhibiting cardiac fibrosis during cardiac remodelling.
Authors: Ayed A Dera; Irfan Ahmad; Prasanna Rajagopalan; Mesfer Al Shahrani; Ahmed Saif; Mohammad Y Alshahrani; Yasser Alraey; Ahmad M Alamri; Sultan Alasmari; Mohammed Makkawi; Ali G Alkhathami; Gaffar Zaman; Abdulrahim Hakami; Razan Alhefzi; Mohammad A Alfhili Journal: Saudi Med J Date: 2021-02 Impact factor: 1.484