Impact of platinum-based chemotherapy on the progression of atherosclerosis.
OBJECTIVE
Although patients with gynecological malignancies now survive longer due to advances in early diagnosis and therapy, major issues still remain regarding the quality of life for the survivors. Surgical menopause increases the risk of atherosclerosis; however, few studies have investigated the influence of platinum-based adjuvant chemotherapy. This study was conducted to evaluate the effects of platinum-based chemotherapy on atherosclerosis.


METHODS
This study enrolled 47 women (26 with ovarian cancers and 21 with endometrial cancers) who underwent surgical treatment, with or without platinum-based adjuvant chemotherapy, according to established protocols between 2007 and 2009. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) performed before surgery, and subsequently at 12 months after treatment. The flow-mediated dilatation of the brachial artery was measured before and immediately following chemotherapy to evaluate the vascular endothelial damage. Human umbilical vein endothelial cells (HUVECs) were used to evaluate cisplatin-induced vascular endothelial dysfunction in vitro.


RESULTS
Although there were no significant differences in the baPWV associated with surgical treatment, platinum-based chemotherapy was associated with an increased baPWV. Significant decreases of flow-mediated dilatation were observed immediately following chemotherapy. An in vitro examination demonstrated that cisplatin attenuated nitric oxide production via inhibition of Akt-eNOS cascades in HUVECs.


CONCLUSIONS
This research suggests that platinum-based chemotherapy directly induces vascular endothelial dysfunction and may be a risk factor for the development of atherosclerosis. Therefore, gynecologic cancer survivors should be educated about these potential risks, and informed regarding lifestyle modifications that may benefit their general health.
Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-city, Osaka, Japan.
T
T
Sekijima
A
A
Tanabe
R
R
Maruoka
N
N
Fujishiro
S
S
Yu
S
S
Fujiwara
H
H
Yuguchi
Y
Y
Yamashita
Y
Y
Terai
M
M
Ohmichi
D055109:Ankle Brachial Index; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000503:physiopathology*; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000000981:diagnostic imaging; D000001:Calcimycin / Q000494:pharmacology; D016190:Carboplatin / Q000627:therapeutic use; D002478:Cells, Cultured; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use*; D016889:Endometrial Neoplasms / Q000628:therapy; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000628:therapy; D017239:Paclitaxel / Q000627:therapeutic use; D010766:Phosphorylation; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography; D014471:Umbilical Veins / Q000166:cytology
D000970:Antineoplastic Agents; D007476:Ionophores; D014280:Triglycerides; D000001:Calcimycin; D016190:Carboplatin; D052250:Nitric Oxide Synthase Type III; D051058:Oncogene Protein v-akt; D017239:Paclitaxel; D002945:Cisplatin