AAV9-Mediated Cardiac CNTF Overexpression Exacerbated Adverse Cardiac Remodeling in Streptozotocin-Induced Type 1 Diabetic Models

• Published in: Cardiovascular toxicology Vol. 22; no. 1; pp. 88 - 96
• Main Authors: Zhong, Peng, Peng, Jianye, Liu, Tao, Ding, Hua-sheng
• Format: Journal Article
• Language: English
• Published: New York Springer US 2022; Springer; Springer Nature B.V
• Subjects: Analysis; Animal models; Animal tissues; Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cardiology; Cardiomyocytes; Ciliary neurotrophic factor; Ciliary Neurotrophic Factor - genetics; Ciliary Neurotrophic Factor - metabolism; Cytokines - genetics; Cytokines - metabolism; Dependovirus - genetics; Dependovirus - metabolism; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Type 1 - chemically induced; Diabetes Mellitus, Type 1 - complications; Diabetic Cardiomyopathies - etiology; Diabetic Cardiomyopathies - genetics; Diabetic Cardiomyopathies - metabolism; Diabetic Cardiomyopathies - physiopathology; Female; Fibrosis; Gene transfer; Gene Transfer Techniques; Genes; Genetic Vectors; Heart; Inflammation; Inflammation Mediators; Inflammatory response; Mice; Mice, Inbred C57BL; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Pharmacology/Toxicology; Rodents; Streptozocin; Type 1 diabetes; Up-Regulation; Ventricle; Ventricular Remodeling; Viruses; CNTF; Inflammation; Diabetes; Cardiac remodeling
• ISSN: 1530-7905; 1559-0259
• DOI: 10.1007/s12012-021-09706-6

Ciliary neurotrophic factor (CNTF), which is a neural peptide, has been reported to confer cardioprotective effects. However, whether CNTF-based gene delivery could prevent cardiac remodeling in diabetes mellitus remains unknown. In this study, we used adeno-associated viral vector serotype 9 (AAV9)-based cardiac gene delivery to test the effects of CNTF overexpression on adverse ventricular remodeling in streptozotocin-induced type 1 diabetic mice models. Postnatal (P3-P10) mice were peritoneally injected with AAV9 recombinant virus carrying the CNTF gene or EGFP gene. Then, type 1 diabetic models were established by peritoneal injection of streptozotocin (200 mg/kg) in 7-week-old female mice injected with AAV9. 4 weeks later after the establishment of type 1 diabetes mellitus, mouse hearts were removed to assess the degree of cardiac remodeling. We found that CNTF overexpression in mouse cardiomyocytes exacerbated cell apoptosis and cardiac fibrosis coupled with an increased inflammatory response in the heart tissue of diabetic female mice. Taken together, our results suggested that cardiac CNTF gene delivery may not be beneficial in alleviating adverse cardiac remodeling in type 1 diabetes female mice.