Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles

OBJECTIVE: The toxicity of anti-cancer chemotherapeutic agents can be reduced by associating these compounds, such as the anti-proliferative agent paclitaxel, with a cholesterol-rich nanoemulsion (LDE) that mimics the lipid composition of low-density lipoprotein (LDL). When injected into circulation, the LDE concentrates the carried drugs in neoplastic tissues and atherosclerotic lesions. In rabbits, atherosclerotic lesion size was reduced by 65% following LDE-paclitaxel treatment. The current study aimed to test the effectiveness of LDE-paclitaxel on inpatients with aortic atherosclerosis. METHODS: This study tested a 175 mg/m2 body surface area dose of LDE-paclitaxel (intravenous administration, 3/3 weeks for 6 cycles) in patients with aortic atherosclerosis who were aged between 69 and 86 yrs. A control group of 9 untreated patients with aortic atherosclerosis (72-83 yrs) was also observed. RESULTS: The LDE-paclitaxel treatment elicited no important clinical or laboratory toxicities. Images were acquired via multiple detector computer tomography angiography (64-slice scanner) before treatment and at 1-2 months after treatment. The images showed that the mean plaque volume in the aortic artery wall was reduced in 4 of the 8 patients, while in 3 patients it remained unchanged and in one patient it increased. In the control group, images were acquired twice with an interval of 6-8 months. None of the patients in this group exhibited a reduction in plaque volume; in contrast, the plaque volume increased in three patients and remained stable in four patients. During the study period, one death unrelated to the treatment occurred in the LDE-paclitaxel group and one death occurred in the control group. CONCLUSION: Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size.

Aterosclerose: diagnóstico macroscópico nas autópsias / Atherosclerosis: macroscopic diagnosis at autopsy

O diagnóstico macroscópico da aterosclerose nas autópsias é essencial; por ser um processo inflamatório crônico do leito arterial, tem graves consequências para o aparelho circulatório, tendo como resultado o infarto cerebral isquêmico, hemorragias encefálicas, infarto agudo do miocárdio, arteropatias, aneurismas, cardiopatias isquêmicas e morte súbita. Fatores de risco genéticos e ambientais influenciam fortemente seu surgimento. Seu diagnóstico macroscópico durante as autópsias é condição sine qua non para entender a sequência de eventos fisiopatológicos que levaram ao óbito, permitindo a identificação da causa mortis.