INTRODUCTION: MiR-195 has been implicated in the development of abdominal aortic aneurysms (AAA). However, the underlying mechanisms have not been fully addressed. AIM: To explore the roles of miR-195 in regulating the proliferation and apoptosis of vascular smooth muscle cells (VSMCs), as well as its molecular basis in vitro. METHODS: qRT-PCR was used to determine the expression levels of miR-195 and Smad3 in aortic media specimens or VSMCs. Western blot was performed to detect the protein levels of Smad3, osteopontin (OPN), and collagen III in aortic media specimens and VSMCs. Luciferase reporter assay was applied to confirm the target of miR-195 in VSMCs. Proliferation and apoptosis of VSMCs were measured by MTT and flow cytometry, respectively. RESULTS: In comparison with the normal controls, the levels of miR-195, OPN, and collagen III were significantly increased in AAA tissue. Smad3 was validated to be a direct target of miR-195. miR-195 inhibited proliferation and induced apoptosis of VSMCs, which was abated by Smad3 overexpression. Expression of OPN and collagen III was improved in VSMCs after transfection with miR-195 mimics, while up-regulation of Smad3 reversed this effect. CONCLUSION: MiR-195 promotes media remodeling by targeting Smad3 in AAA progression. This study suggests that miR-195 contributes to the pathogenesis of AAA and reveals a new targeted therapy strategy for AAA patients.
INTRODUCTION:MiR-195 has been implicated in the development of abdominal aortic aneurysms (AAA). However, the underlying mechanisms have not been fully addressed. AIM: To explore the roles of miR-195 in regulating the proliferation and apoptosis of vascular smooth muscle cells (VSMCs), as well as its molecular basis in vitro. METHODS: qRT-PCR was used to determine the expression levels of miR-195 and Smad3 in aortic media specimens or VSMCs. Western blot was performed to detect the protein levels of Smad3, osteopontin (OPN), and collagen III in aortic media specimens and VSMCs. Luciferase reporter assay was applied to confirm the target of miR-195 in VSMCs. Proliferation and apoptosis of VSMCs were measured by MTT and flow cytometry, respectively. RESULTS: In comparison with the normal controls, the levels of miR-195, OPN, and collagen III were significantly increased in AAA tissue. Smad3 was validated to be a direct target of miR-195. miR-195 inhibited proliferation and induced apoptosis of VSMCs, which was abated by Smad3 overexpression. Expression of OPN and collagen III was improved in VSMCs after transfection with miR-195 mimics, while up-regulation of Smad3 reversed this effect. CONCLUSION:MiR-195 promotes media remodeling by targeting Smad3 in AAA progression. This study suggests that miR-195 contributes to the pathogenesis of AAA and reveals a new targeted therapy strategy for AAA patients.
Authors: Emma Plana; Laura Gálvez; Pilar Medina; Silvia Navarro; Victoria Fornés-Ferrer; Joaquín Panadero; Manuel Miralles Journal: Int J Mol Sci Date: 2020-06-28 Impact factor: 5.923
Authors: Karlijn B Rombouts; Tara A R van Merrienboer; Johannes C F Ket; Natalija Bogunovic; Jolanda van der Velden; Kak Khee Yeung Journal: Eur J Clin Invest Date: 2021-11-21 Impact factor: 5.722