Angiotensin receptor blockers and statins could alleviate atrial fibrosis via regulating platelet-derived growth factor/Rac1/nuclear factor-kappa B Axis.

Abstract

AIMS:

To investigate whether the administration of renin-angiotensin system (RAS) inhibitors and statins could alleviate atrial fibrosis via platelet-derived growth factor (PDGF)/Rac1 /nuclear factor-kappa B (NF-κB) axis.

METHODS AND RESULTS:

In human left atrium, the degree of atrial fibrosis, as well as the expression levels of PDGF, Rac1 and NF-κB increased 1.5 to 2.9 folds in patients with atrial fibrillation compared to that with sinus rhythm, (P<0.0001). There were strongly positive correlations between angiotensin II (Ang II) or procollagen type III-alpha-1 (COL3A1) with PDGF, Rac1, NF-κB, and among PDGF, Rac1 and NF-κB (all P<0.05). At 3 weeks after the transverse aorta constriction (TAC) operation in rat model and with intervention of irbesartan or/and simvastatin, the collagen volume fraction (CVF) and atrial natriuretic peptide (ANP) values respectively increased 6-folds and 3.5-folds in the TAC group compared to SHAM group (P<0.0001), but these levels decreased by 16% to 63% with following drug intervention (all P<0.0001), the combined treatment was the lowest. Accordingly, the expression levels of PDGF (3-folds), Rac1 (1.6-folds), NF-κB (7-folds) and AngII (12-folds) significantly increased in the TAC group compared to the SHAM group, and these levels were also reduced by 25% to 64% with following drug intervention. The highest reduction could be seen after treatment with irbesartan and simvastatin in combination (all P<0.001).There were strongly positive correlations between AngII or CVF with PDGF, Rac1, NF-κB, and among PDGF, Rac1 and NF-κB (all P<0.05).

CONCLUSIONS:

Irbesartan or/and simvastatin can improve atrial fibrosis by regulating PDGF/Rac1/NF-κB axis.

• Authors: Dongfang Yang, Jia Yuan, Gan Liu, Zhiyu Ling, Haiyan Zeng, Yunqing Chen, Yue Zhang, Qiang She, Xue Zhou
• Journal: International journal of medical sciences (Int J Med Sci) Vol. 10 Issue 7 Pg. 812-24 ( 2013) ISSN: 1449-1907 [Electronic] Australia
• PMID: 23794945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin Receptor Antagonists
• DNA Primers
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• NF-kappa B
• Platelet-Derived Growth Factor
• Angiotensin II
• rac1 GTP-Binding Protein

Topics

• Angiotensin II (metabolism)
• Angiotensin Receptor Antagonists (pharmacology)
• Animals
• Base Sequence
• DNA Primers
• Electrophoretic Mobility Shift Assay
• Enzyme-Linked Immunosorbent Assay
• Heart Atria (drug effects, metabolism, pathology)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• NF-kappa B (metabolism)
• Platelet-Derived Growth Factor (metabolism)
• Rats
• Reverse Transcriptase Polymerase Chain Reaction
• rac1 GTP-Binding Protein (metabolism)