New TLR4 and TLR2 detection method from peripheral human blood for early detection of doxorubicin-induced cardiotoxicity

Introduction: Cancer treatments can have significant cardiovascular adverse effects that can cause cardi-omyopathy and heart failure with reduced survival be-nefit and considerable decrease in the use of antineo-plastic therapy.

Objective: The purpose of this study is to assess the role of TLR2 and TLR4 gene expression as an early marker for the risk of doxorubicin-induced cardiomyopathy in correlation with early diastolic dysfunction in patients treated with doxorubicin.

Methods: Our study included 25 consecutive patients who received treatment with doxorubicin for hemato-logical malignancies (leukemia, lymphomas or mul-tiple myeloma), aged 18–65 years, with a probability survival >6 months and with left ventricular ejecti-on fraction >50%. Exclusion criteria consisted of the following: previous anthracycline therapy, previous radiotherapy, history of heart failure or chronic renal failure, atrial fibrillation, and pregnancy. In all pati-ents, in fasting state, a blood sample was drawn for the assessment of TLR2 and TLR4 gene expression. Gene expression was assessed by quantitative reverse tran-scription PCR (qRT-PCR) using blood collection, RNA isolation, cDNA reverse transcription, qRT-PCR and quantification of the relative expression. At enrollment, all patients were evaluated clinically; an ECG and an echocardiography were performed.

Results: The average amount of gene expression units was 0.113 for TLR4 (range 0.059–0.753) and 0.218 for TLR2 (range 0.046 – 0.269). The mean mRNA extracted quantity was 113 571 ng/μl. As for the diastolic functi-on parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean values for TLR4 were 0.1198625 and for TLR2 were 0.16454 gene expression units. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean value for TLR2 was 0.30 ± 0.19 and for TLR4 was 0.15 ± 0.04. The corres-ponding values for the patients who did not develop di-astolic dysfunction were 0.16 ± 0.07 for TLR2 (P=0.01) and 0.11 ± 0.10 for TLR4 (P=0.2).

Conclusions: Our study suggests that TLR4 and TLR2 expression is higher in patients under doxorubicin therapy, those who develop diastolic dysfunction. This may suggest a predisposition to myocardial involve-ment of TLR2 and TLR4 hiper-expression, translated into a higher sensitivity to doxorubicin cardiac effects.

ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
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CODE: 379
CME Credits: 10 (Romanian College of Physicians)