Back to Search
Start Over
TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling
- Source :
- Heart and Vessels
- Publication Year :
- 2018
- Publisher :
- Springer Japan, 2018.
-
Abstract
- Sinoatrial node fibrosis is involved in the pathogenesis of sinus sick syndrome (SSS). Transient receptor potential (TRP) subfamily M member 7 (TRPM7) is implicated in cardiac fibrosis. However, the mechanisms underlying the regulation of sinoatrial node (SAN) fibrosis in SSS by TRPM7 remain unknown. The aim of this study was to investigate the role of angiotensin II (Ang II)/TRPM7/Smad pathway in the SAN fibrosis in rats with SSS. The rat SSS model was established with sodium hydroxide pinpoint pressing permeation. Forty-eight rats were randomly divided into six groups: normal control (ctrl), sham operation (sham), postoperative 1-, 2-, 3-, and 4-week SSS, respectively. The tissue explant culture method was used to culture cardiac fibroblasts (CFs) from rat SAN tissues. TRPM7 siRNA or encoding plasmids were used to knock down or overexpress TRPM7. Collagen (Col) distribution in SAN and atria was assessed using PASM–Masson staining. Ang II, Col I, and Col III levels in serum and tissues or in CFs were determined by ELISA. TRPM7, smad2 and p-smad2 levels were evaluated by real-time PCR, and/or western blot and immunohistochemistry. SAN and atria in rats of the SSS groups had more fibers and higher levels of Ang II, Col I and III than the sham rats. Similar findings were obtained for TRPM7 and pSmad2 expression. In vitro, Ang II promoted CFs collagen synthesis in a dose-dependent manner, and potentiated TRPM7 and p-Smad2 expression. TRPM7 depletion inhibited Ang II-induced p-Smad2 expression and collagen synthesis in CFs, whereas increased TRPM7 expression did the opposite. SAN fibrosis is regulated by the Ang II/TRPM7/Smad pathway in SSS, indicating that TRPM7 is a potential target for SAN fibrosis therapy in SSS.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Cardiac fibrosis
Blotting, Western
Sick sinus syndrome
TRPM7
TRPM Cation Channels
Enzyme-Linked Immunosorbent Assay
SMAD
Smad2 Protein
030204 cardiovascular system & hematology
Sinoatrial node
Real-Time Polymerase Chain Reaction
Pathogenesis
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Western blot
Fibrosis
Internal medicine
medicine
Animals
Cells, Cultured
Cell Proliferation
medicine.diagnostic_test
business.industry
Angiotensin II
Myocardium
medicine.disease
Immunohistochemistry
Rats
SSS
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
RNA
Original Article
Female
Collagen
Cardiology and Cardiovascular Medicine
business
Smad2
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 16152573 and 09108327
- Volume :
- 33
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Heart and Vessels
- Accession number :
- edsair.doi.dedup.....88e14de6a3abf392118a32f4d9ba66be