The study of chemotherapy associated cardiovascular dysfunction

Abstract

Cancer, the disease, challenges the uniquely controlled programme of life. According to the World Health Organization, it tolls over 9.6 million deaths worldwide in 2018. The scientific and technological advancements of cancer therapy lead to an excessive number of long-term cancer survivors. However, their quality of life is compromised due to the collateral damages caused by chemotherapy. Chemotherapy Associated Cardiovascular Dysfunction (CACD) includes a diverse range of Cardiovascular Diseases (CVD) like hypertension, atherosclerosis, pericarditis, coronary heart disease, cardiac ischemia, cardiac arrhythmia, and congestive heart failure resulting in poor vascular health even death. Due to the lack of complete understanding of the multi-factorial cellular and molecular drivers underlying CACD, the optimal therapeutic approaches for the protection against it have not been formulated precisely. In the present study, we aim to secure the quality of life for cancer survivors by developing early diagnostic marker of cardiovascular damage. It is well established that Nitric Oxide (NO) produced by Red blood cell NO synthase (RBC NOS) plays an important role in maintaining cardiovascular homeostasis and hence it is of our interest to study the dynamics of RBC NOS under chemotherapy. We further plan to employ a novel in-silico method combined with experimental validation to explore offtargets of chemotherapeutic drugs and prioritize the enriched molecular pathways related to the specific cardiovascular events by deriving the relationship between drug-target-pathways and cardiovascular complications. The cancer patients just diagnosed (n = 66) and chemo-treated cancer patient (n = 66), attending the outpatient clinic of Department of Surgical Oncology, Rajiv Gandhi Government General Hospital, Chennai, India since January 2016 were included in our study. We found an increased number of individuals with hypertension and abnormal ECG among chemotherapy-treated cancer patients compared to cancer patients without any type of treatment. We observed a significantly increased Lactate dehydrogenase (LDH) activity and endothelin content in plasma of cancer patients treated with chemotherapy compared to the other groups, thus indicating that there was significant cell damage in chemotherapy-treated patients. Results indicated that there was a significant increase in Nitrite, Von Willebrand factor (vWF), and Malondialdehyde (MDA) level in plasma of chemotherapy-treated patients compared to untreated cancer patients and healthy control. Thus, we detected the molecular factors of vascular dysfunction along with the high oxy-nitrosative stress in chemo-treated cancer patient that could lead to cardiovascular dysfunction associated with chemotherapy newline