Billel Chaouad1, Elara N Moudilou2, Adel Ghoul3, Fouzia Zerrouk3, Anissa Moulahoum3, Khira Othmani-Mecif3, Mohamed El Hadi Cherifi4, Jean-Marie Exbrayat2, Yasmina Benazzoug5. 1. Biochemistry and Remodeling of the Extracellular Matrix, Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, Houari Boumediene University of Science and Technology (USTHB), Bab Ezzouar, El Alia, 16111, Algiers, Algeria; University Djilali Bounaama of Khemis Miliana, Faculty of Natural and Life Sciences and Earth Sciences, Theniet El Had Road, 44225, Khemis Miliana, Algeria. 2. UMRS 449, General Biology - Reproduction and Comparative Development, Lyon Catholic University, UDL, EPHE, PSL, 10, Place des Archives, 69288, Lyon Cedex 02, France. 3. Biochemistry and Remodeling of the Extracellular Matrix, Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, Houari Boumediene University of Science and Technology (USTHB), Bab Ezzouar, El Alia, 16111, Algiers, Algeria. 4. Central Laboratory of Biology, EPH Bologhine Ibn Ziri, Algiers, Algeria. 5. Biochemistry and Remodeling of the Extracellular Matrix, Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, Houari Boumediene University of Science and Technology (USTHB), Bab Ezzouar, El Alia, 16111, Algiers, Algeria. Electronic address: ybenazzoug@usthb.dz.
Abstract
OBJECTIVE: Numerous studies have shown that a methionine-rich diet induces hyperhomocysteinemia (Hhcy), a risk factor for cardiovascular diseases. The objective of the present study was to determine the involvement of Hhcy in cardiac remodeling in the sand rat Psammomys obesus. MATERIALS AND METHODS: An experimental Hhcy was induced, in the sand rat Psammomys obesus, by intraperitoneal injection of 300 mg/kg of body weight/day of methionine for 1 month. The impact of Hhcy on the cellular and matricial structures of the myocardium was analyzed with histological techniques (Masson trichrome and Sirius red staining). Immunohistochemistry allowed us to analyze several factors involved in myocardial remodeling, such as fibrillar collagen I and III, metalloproteases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2), TGF-β1 and activated caspase 3. RESULTS: Our results show that Hhcy induced by an excess of methionine causes, in the myocardium of Psammomys obesus, a significant accumulation of fibrillar collagens I and III at the interstitial and perivascular scales, indicating the appearance of fibrosis, which is associated with an immuno-expression increase of TGF-β1, MMP-9 and TIMP-2 and an immuno-expression decrease of MMP-2 and TIMP-1. Also, Hhcy induces apoptosis of some cardiomyocytes and cardiac fibroblasts by increasing of activated caspase 3 expression. These results highlight a remodeling of cardiac tissue in hyperhomocysteinemic Psammomys obesus.
OBJECTIVE: Numerous studies have shown that a methionine-rich diet induces hyperhomocysteinemia (Hhcy), a risk factor for cardiovascular diseases. The objective of the present study was to determine the involvement of Hhcy in cardiac remodeling in the sand ratPsammomys obesus. MATERIALS AND METHODS: An experimental Hhcy was induced, in the sand ratPsammomys obesus, by intraperitoneal injection of 300 mg/kg of body weight/day of methionine for 1 month. The impact of Hhcy on the cellular and matricial structures of the myocardium was analyzed with histological techniques (Masson trichrome and Sirius red staining). Immunohistochemistry allowed us to analyze several factors involved in myocardial remodeling, such as fibrillar collagen I and III, metalloproteases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2), TGF-β1 and activated caspase 3. RESULTS: Our results show that Hhcy induced by an excess of methionine causes, in the myocardium of Psammomys obesus, a significant accumulation of fibrillar collagens I and III at the interstitial and perivascular scales, indicating the appearance of fibrosis, which is associated with an immuno-expression increase of TGF-β1, MMP-9 and TIMP-2 and an immuno-expression decrease of MMP-2 and TIMP-1. Also, Hhcy induces apoptosis of some cardiomyocytes and cardiac fibroblasts by increasing of activated caspase 3 expression. These results highlight a remodeling of cardiac tissue in hyperhomocysteinemic Psammomys obesus.