Abstract 101: Transforming Growth Factor-Beta-Receptor Antagonist Blocks the Cardiac Fibrosis and Remodeling in Guanylyl Cyclase/Natriuretic Peptide Receptor-A Gene-Disrupted Mice

Hypertension ◽  
2018 ◽  
Vol 72 (Suppl_1) ◽  
Author(s):  
Umadevi Subramanian ◽  
Ramachandran Samivel ◽  
Hanqing Zhao ◽  
Venkateswara Gogulamudi ◽  
Kailash N Pandey
Keyword(s):  
Growth Factor ◽  
Receptor Antagonist ◽  
Guanylyl Cyclase ◽  
Transforming Growth Factor Beta ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A ◽  
Growth Factor Beta

scholarly journals MicroRNA-210-5p Alleviates Cardiac Fibrosis via Targeting Transforming Growth Factor-beta Type I Receptor in Rats on High Salt Diet

2021 ◽  
Author(s):  
Kun Zhao ◽  
Yukang Mao ◽  
Xiaoman Ye ◽  
Jiazheng Ma ◽  
Litao Sun ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Collagen I ◽  
Type I ◽  
High Salt Diet ◽  
Salt Diet ◽  
Growth Factor Beta

Abstract Background: The aim of the present study was to explore whether high salt diet (HSD) caused cardiac fibrosis regardless of blood pressure in rats, and to determine the effects of microRNA (miR)-210-5p on sodium chloride (NaCl)-induced fibrosis in neonatal rat cardiac fibroblasts (NRCFs) and its target. Methods: The rats received 8% HSD in vivo, and NRCFs were treated with NaCl in vitro. Results: The levels of collagen I, alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-β) were increased in the heart of hypertension (HTN), hypertension-prone (HP) and hypertension-resistant (HR) rats on HSD. Middle and high doses (50 mM and 100 mM) of NaCl increased the levels of collagen I, α-SMA and TGF-β in NRCFs. The expression level of miR-210-5p was reduced in NaCl-treated NRCFs by miR high-throughput sequencing. The NaCl-induced increases of collagen I, α-SMA and TGF-β were inhibited by miR-210-5p agomiR, and further enhanced by miR-210-5p antagomiR. Bioinformatics analysis and luciferase reporter assays demonstrated that TGF-β type I receptor (TGFβRI) was a direct target gene of miR-210-5p. These results indicated that HSD resulted in cardiac fibrosis regardless of blood pressure. Conclusion: The upregulation of miR-210-5p could attenuate NRCF fibrosis via targeting TGFβRI. Thus, upregulating miR-210-5p to inhibit TGF-β signaling pathway might be a strategy for the treatment of cardiac fibrosis.

Abstract 78: Transforming Growth Factor-β Induces the Cardiac Fibrosis and Remodeling in Guanylyl cyclase/Natriuretic Peptide Receptor-A Gene-Disrupted Null Mutant Mice

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Kailash N Pandey ◽  
Umadevi Subramanian
Keyword(s):  
Growth Factor ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Left Ventricular ◽  
Null Mutant ◽  
Wild Type ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A ◽  
Β Receptor ◽  
Null Mutant Mice

Genetic disruption of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) in mice exhibits high blood pressure, cardiac hypertrophy, fibrosis, and remodeling leading to congestive heart failure. The objective of this study was to determine the mechanisms regulating the development of fibrosis in Npr1 gene-disrupted mice hearts. The Npr1 null mutant (Npr1-/-, 0-copy), heterozygous (Npr1+/-, 1-copy), and wild-type (Npr1+/+, 2-copy) mice were administered by oral gavage with transforming growth factor-β1 (TGF- β1) receptor inhibitor GW788388 (1mg/kg/day) for 28 days. The heart tissues were isolated and used for quantification of fibrotic markers by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot analyses. Together, systolic blood pressure (SBP), heart weight-to-body weight (HW/BW) ratio, left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVEDS), and percent fractional shortening (FS) were analyzed. The Npr1-/- null mutant mice hearts displayed 6-fold induction of fibrosis compared with wild-type (WT) Npr1+/+ mice. Furthermore, the increased expression of fibrotic markers as observed, including connective tissue growth factor (CTGF, 5-fold), α-smooth muscle actin (α-SMA, 4-fold) and TGF-β receptor I (TGF-βRI, 4-fold), TGF-β receptor II (TGF-βRII, 3.5-fold) and Smad2/3 proteins in Npr1-/- mice hearts compared with WT control mice. However, treatment with TGF-β receptor antagonist, GW788388, significantly prevented the cardiac fibrosis and down-regulated the expression of fibrotic markers and Smad proteins in Npr1-/- mice compared to vehicle-treated WT controls. The results of the present study suggest that the activation of cardiac fibrosis in Npr1-/- mice is mainly triggered through TGF-β mediated Smad-dependent pathways.

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