Imatinib Mesylate Attenuates Cardiac Fibrosis in Spontaneously Hypertensive Rats.
10.5646/jksh.2011.17.2.48
- Author:
Eun Ho CHOO
1
;
Sang Hyun IHM
;
Ok Ran KIM
;
Sung Won JANG
;
Chan Seok PARK
;
Hee Yeol KIM
;
Kiyuk CHANG
;
Ho Joong YOUN
;
Wook Sung CHUNG
;
Ki Bae SEUNG
;
Jae Hyeong KIM
Author Information
1. Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea. limsh@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Rats, Inbred SHR;
Imatinib, Fibrosis;
Echocardiography;
Diastole
- MeSH:
Animals;
Benzamides;
Blood Pressure;
Collagen;
Diastole;
Echocardiography;
Echocardiography, Doppler;
Fibroblasts;
Fibrosis;
Heart;
Heart Diseases;
Hemodynamics;
Humans;
Immunoblotting;
Leukemia;
Male;
Mesylates;
Phosphorylation;
Phosphotransferases;
Piperazines;
Platelet-Derived Growth Factor;
Protein-Tyrosine Kinases;
Pyrimidines;
Rats;
Rats, Inbred SHR;
RNA, Messenger;
Tyrosine;
Imatinib Mesylate
- From:Journal of the Korean Society of Hypertension
2011;17(2):48-56
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Hypertensive myocardial fibrosis promotes abnormalities of cardiac function that may adversely affect the clinical outcome of hypertensive patients. Imatinib mesylate blocks receptor tyrosine kinase and is clinically used to treat leukemia. Platelet-derived growth factor (PDGF) is a downstream target of receptor tyrosine kinases. Cardiac fibroblasts can be activated by PDGF. Thus we evaluated whether imatinib attenuate myocardial fibrosis and prevents diastolic dysfunction in spontaneously hypertensive rats (SHR). METHODS: 8 weeks old male SHRs were subjected to treatment with 8 weeks of low dose imatinib (SHR-10; 10 mg/kg), high dose imatinib (SHR-30; 30 mg/kg) or saline (SHR-C; n = 6 in each group). At the age of 16 weeks, all rats underwent hemodynamic studies and Doppler echocardiography, and were sacrificed. Their hearts were extracted for histopathological, immunoblotting and quantitative reverse transcriptase-polymerase chain reaction analyses. RESULTS: While imatinib did not affect blood pressure (BP), it markedly reduced perivascular and interstitial fibrosis in the hearts of SHR. Echocardigram showed that high-dose imatinib significantly reduced left ventricular (LV) wall thickness (septal/posterior wall; SHR-C vs. SHR-30: 18 +/- 2/19 +/- 2 mm vs. 15 +/- 1/14 +/- 1 mm; p < 0.05) and improved the parameters of LV diastolic function such as E/A ratio (SHR-C vs. SHR-30: 1.60 +/- 0.10 vs. 1.86 +/- 0.20; p < 0.05). Imatinib also significantly reduced mRNA expression of collagen III and PDGF beta-receptor tyrosine phosphorylation in the hearts of SHR. CONCLUSIONS: These results suggest that imatinib, especially high dose, could attenuate myocardial fibrosis and prevent LV diastolic dysfunction in hypertensive rat model by decreased activity of PDGF. Imatinib may provide a potential therapeutic approach for hypertensive heart disease.
