Imatinib Mesylate Attenuates Myocardial Remodeling Through Inhibition of Platelet-Derived Growth Factor and Transforming Growth Factor Activation in a Rat Model of Hypertension

Imatinib mesylate is a specific tyrosine kinase inhibitor that may block the platelet-derived growth factor and transforming growth factor pathways. These pathways are known to provoke fibroblast activation. We evaluated whether imatinib, by inhibiting these pathways, prevents diastolic dysfunction and attenuates myocardial remodeling using spontaneously hypertensive rats (SHRs). Eight-week-old male SHRs were randomly assigned to either imatinib treatment group (30 mg/kg per day; n=10; SHR-I) or hypertensive control group (distilled water, n=10; SHR-C). Wistar-Kyoto rats were used as normal controls (n=10). At 16 weeks, all rats underwent hemodynamic studies and Doppler echocardiography and then were euthanized. Their hearts were extracted for histopathologic, immunoblotting, and quantitative reverse transcriptase polymerase chain reaction analyses. Although imatinib did not affect blood pressure, it markedly reduced perivascular and interstitial fibrosis in the hearts of SHR. Echocardiogram showed that imatinib significantly reduced the left ventricular wall thickness (septal/posterior wall; SHR-C versus SHR-I, 18±1/19±2 versus 15±1/15±1 mm; P