Endothelial Injury as a Potential Contributor to Cardiovascular Toxicity in Hematologic Malignancies.

Abstract

Cardiovascular toxicity is an important complication of treatment for hematologic malignancies, but it is often discussed mainly in terms of direct myocardial injury. Endothelial injury may provide a common link between several cardiovascular complications seen in these patients. Endothelial dysfunction may already be present because of the malignancy itself and can be further increased by anticancer treatment, immune activation and haematopoietic stem cell transplantation. Oxidative stress, reduced nitric oxide availability, inflammation, increased vascular permeability and activation of coagulation can shift the endothelium from a protective to a pro-inflammatory and prothrombotic state. These changes could contribute to hypertension, thrombosis, atherosclerotic disease, coronary microvascular dysfunction, arterial stiffness and myocardial dysfunction. The role of endothelial injury is particularly relevant with BCR-ABL inhibitors, proteasome inhibitors, CAR-T-cell therapy, bispecific antibodies and transplantation, although the mechanisms and strength of evidence differ between treatments. Several circulating biomarkers and tools, including angiopoietin-2, von Willebrand factor, soluble thrombomodulin, adhesion molecules and the Endothelial Activation and Stress Index, may help identify endothelial injury, but their clinical roles still remain unclear. This review examines endothelial injury across hematologic malignancies and their treatments and discusses its role in cardiovascular toxicity, current approaches to vascular protection and the main gaps that need to be addressed before endothelial assessment can become part of routine cardio-oncology care.