The Effect of Intravenous Administration of Alprostadil on Circulating Microvesicles in Patients with Chronic Limb-Threatening Ischemia (CLTI): A Preliminary Study

Background/Objectives: The treatment of patients with advanced peripheral arterial disease, such as chronic limb-threatening ischemia (CLTI), often requires more than the use of conventional vasodilators and revascularization procedures, when these are feasible. Alprostadil is typically administered intravenously to treat these patients. However, existing studies reported conflicting results regarding the efficacy of the aforementioned treatment. It is hypothesized that, based on clinical experience, this therapy may exhibit a benefit for patients with CLTI, promoting ulcer healing, alleviating pain, and improving limb salvage rates. Consequently, the concept of employing blood-circulating microvesicles (MVs) as biomarkers for evaluating treatment effectiveness and estimating clinical prognoses has been proposed. Methods: These were analyzed in a group of patients with CLTI before and during alprostadil treatment, with and without revascularization procedures, to assess their correlation with clinical outcomes. Results: Our data indicated that CLTI results in an increase in circulating levels of MVs, as well as in specific subtypes of plasma MVs—MVs derived from endothelial cells (EMVs), platelets (PMVs), leukocytes (LeMVs), monocytes (MMVs), and erythrocytes (ErMVs)—compared to levels observed in the plasma of healthy individuals. Furthermore, treatment with alprostadil was associated with a significant reduction in plasma levels of total MVs, as well as EMVs, PMVs, LeMVs, and MMVs. In contrast, revascularization procedures do not appear to result in a reduction in circulating MV levels. These results are consistent with the clinical improvements observed in CLTI patients treated with alprostadil. Conclusions: In summary, the findings of this preliminary study suggest that blood-circulating MVs, including specific subtypes such as EMVs, PMVs, LeMVs, and MMVs, may have potential as biomarkers for assessing the response to alprostadil treatment in patients with CLTI.