Myocardial expression of PDECGF is associated with extracellular matrix remodeling in experimental myocardial infarction in rats

Hemalatha, Thiagarajan; Balachandran, C.; Manohar, B. Murali; Nayeem, Mohammed; Subramaniam, Samu; Sharma, Hari Shankar; Puvanakrishnan, Rengarajulu

doi:10.1139/o09-165

Cited by 14 publications

(15 citation statements)

References 32 publications

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“…Thymidine phosphorylase is an enzyme involved in the conversion of capecitabine into 5-fluorouracil and of 5-fluorouracil into its active metabolites; the enzyme is an angiogenic factor 55,56 whose expression is upregulated in atherosclerotic plaques and during myocardial infarction. 21,22 Toxic effects of the drugs could also be caused through endothelial damage, with increased levels of endothelin 1 producing vasospasm and ischemia.…”

Section: Drugs and Mechanismsmentioning

confidence: 99%

Pathophysiology of cardiotoxicity induced by nonanthracycline chemotherapy

Madeddu

Deidda

Piras

et al. 2016

Journal of Cardiovascular Medicine

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The risk and mechanism of chemotherapy-induced cardiotoxicity (CTX) vary depending on the type and intensity of the anticancer regimen. Myriad chemotherapeutic drugs produce adverse cardiovascular effects such as arterial hypertension, heart failure, and thromboembolic events. Among the numerous classes of these drugs, anthracyclines have been studied most extensively because of their overt cardiovascular effects and the high associated incidence of heart failure. However, CTX might also be caused by other types of chemotherapeutic agents, including alkylating agents (cyclophosphamide, ifosfamide), platinum agents, antimetabolites (5-fluorouracil, capecitabine), antibiotics (mitoxantrone, mitomycin, bleomycin), and antimicrotubule agents (taxanes). Here, we review the incidence, clinical impact, and potential mechanisms of CTX associated with nonanthracycline chemotherapy used for cancer patients. The published data support a marked increase in CTX risk, particularly with certain drugs such as 5-fluorouracil and cisplatin. Each anticancer regimen is associated with distinct modes of heart damage, both symptomatic and asymptomatic. However, the underlying mechanisms of CTX have been established only in a few cases, and only few nonanthracycline chemotherapeutics (mitoxantrone, mitomycin, ifosfamide) act through a recognizable mechanism and show a predictable dose dependence. Lastly, nonanthracycline chemotherapy can induce both chronic lesions, such as systolic dysfunction, and acute lesions, such as the ischemia that occurs within hours or days after treatment. An increased understanding of the incidence, mechanisms, and potential therapeutic targets of CTX induced by various nonanthracycline chemotherapeutic agents is clearly required.

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Section: Drugs and Mechanismsmentioning

confidence: 99%

Pathophysiology of cardiotoxicity induced by nonanthracycline chemotherapy

Madeddu

Deidda

Piras

et al. 2016

Journal of Cardiovascular Medicine

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“…TP was also found to be an angiogenic factor (known as platelet-derived endothelial cell growth factor) [ 28 , 29 ]. TP expression is up-regulated in atherosclerotic plaques [ 30 ] and during myocardial infarction [ 31 ], potentially contributing to the higher prevalence of cardiotoxicity in patients with previous cardiovascular disease or 5-FU induced damage.…”

Section: Introductionmentioning

confidence: 99%

Effects of 5-Fluorouracil on Morphology, Cell Cycle, Proliferation, Apoptosis, Autophagy and ROS Production in Endothelial Cells and Cardiomyocytes

et al. 2015

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Antimetabolites are a class of effective anticancer drugs interfering in essential biochemical processes. 5-Fluorouracil (5-FU) and its prodrug Capecitabine are widely used in the treatment of several solid tumors (gastro-intestinal, gynecological, head and neck, breast carcinomas). Therapy with fluoropyrimidines is associated with a wide range of adverse effects, including diarrhea, dehydration, abdominal pain, nausea, stomatitis, and hand-foot syndrome. Among the 5-FU side effects, increasing attention is given to cardiovascular toxicities induced at different levels and intensities. Since the mechanisms related to 5-FU-induced cardiotoxicity are still unclear, we examined the effects of 5-FU on primary cell cultures of human cardiomyocytes and endothelial cells, which represent two key components of the cardiovascular system. We analyzed at the cellular and molecular level 5-FU effects on cell proliferation, cell cycle, survival and induction of apoptosis, in an experimental cardioncology approach. We observed autophagic features at the ultrastructural and molecular levels, in particular in 5-FU exposed cardiomyocytes. Reactive oxygen species (ROS) elevation characterized the endothelial response. These responses were prevented by a ROS scavenger. We found induction of a senescent phenotype on both cell types treated with 5-FU. In vivo, in a xenograft model of colon cancer, we showed that 5-FU treatment induced ultrastructural changes in the endothelium of various organs. Taken together, our data suggest that 5-FU can affect, both at the cellular and molecular levels, two key cell types of the cardiovascular system, potentially explaining some manifestations of 5-FU-induced cardiovascular toxicity.

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“…Increased serum levels of CK isoenzymes variously signal heart, brain, or skeletal muscle damage. They may also be markers for advanced tumours with poor prognosis [49]. Which shown that CK-MB level measured by mass assay, is elevated significantly in serum on day I after myocardial infarction in rats, induced by coronary artery ligation.…”

Section: Variablementioning

confidence: 98%