title: Increased cardiac remodeling in cardiac-specific Flt-1 receptor knockout mice with pressure overload.
abstract: Vascular endothelial growth factor (VEGF) inhibition has previously been shown to have damaging effects on the heart. Because the role of Flt-1 (a phosphotyrosine kinase receptor for VEGF) in cardiac function and hypertrophy is unclear, we generated mice lacking Flt-1 only in their cardiomyocytes (Flt-1 KO). The hearts from 8- to 10-week-old mice were measured by using echocardiography and histology. No significant differences were seen in fraction shortening, cross-sectional area of cardiomyocytes, and interstitial collagen fraction between littermate controls and KO mice at baseline. To test the hypothesis that Flt-1 is involved in cardiac remodeling, we performed transverse aorta constriction (TAC) by ligating the transverse ascending aorta. Four weeks after TAC, echocardiography of the mice was performed, and the hearts were excised for pathological analysis and Western blotting. No difference in mortality was found between Flt-1 KO mice and controls; however, KO mice showed a greater cardiomyocyte cross-sectional area and interstitial collagen fraction than controls. Western blotting indicated that AKT was activated less in Flt-1 KO hearts after TAC compared with that in control hearts. Thus, Flt-1 deletion in cardiomyocytes increased hypertrophy, fibrosis, and regression of AKT phosphorylation. Our study suggests that Flt-1 plays a critical role in cardiac hypertrophy induced by pressure overload via the activation of AKT, which seems to be cardioprotective.
authors.affiliation: Department of Oral Prophylaxis and Hygiene, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People's Republic of China, 325027.
authors.forename: Liqin
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, People's Republic of China, 325027.
authors.forename: Yinqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, People's Republic of China, 325027.
authors.forename: Jiafeng
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, People's Republic of China, 325027. feikey.y@gmail.com.
authors.forename: Maoping
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Cardiology, Tongji Hospital of Tongji University, 309 Xincun Road, Putuo district, Shanghai, People's Republic of China, 200065.
authors.forename: Chaohui
authors.initials: C
authors.lastname: Hu
authors.affiliation: Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, People's Republic of China, 430030.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, People's Republic of China, 325027. wulianpin@gmail.com.
authors.forename: Lianpin
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000473:pathology*; D003251:Constriction, Pathologic; D004452:Echocardiography / Q000379:methods; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000172:deficiency / Q000378:metabolism*
chemical_list: C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: AKT; Cardiac remodeling; Flt-1; Mouse; Pressure overload