# Extracellular Vesicles (EVs) Derived from Senescent Endothelial Cells Promote Platelet Activation

## TL;DR

Senescent endothelial cells release EVs that enhance platelet activation, potentially increasing the risk of blood clots in cancer patients treated with Doxorubicin.

## Contribution

EVs from senescent endothelial cells promote platelet activation independently of their concentration or size.

## Key findings

- Doxorubicin induces senescence and endothelial dysfunction in HMEC-1 cells.
- EVs from senescent cells more strongly activate platelets than those from non-senescent cells.
- EVs alone do not cause platelet aggregation, indicating a need for soluble factors.

## Abstract

Thrombotic cardiovascular diseases are frequent side effects of cancer therapy with cytotoxic drugs such as Doxorubicin. Endothelial cell senescence is emerging as a critical mechanism underlying endothelial dysfunction in this context. Senescent cells, although unable to proliferate, secrete bioactive molecules that alter the tissue microenvironment, a feature known as the senescence-associated secretory phenotype (SASP). Besides soluble molecules, senescent cells also release extracellular vesicles (EVs). Previous studies indicate that senescent endothelial cells produce a secretome that promotes platelet activation; however, the contribution of EVs remains unclear. Here, we show that human microvascular endothelial cells (HMEC-1) exposed to Doxorubicin undergo senescence, display endothelial dysfunction, and release EVs. We found no differences in the concentration or size distribution of EVs from senescent and non-senescent cells. Nevertheless, EVs from senescent HMEC-1 promoted platelet activation more strongly than EVs from control cells. Notably, EVs alone did not induce platelet aggregation, suggesting that soluble factors are also required to support platelet-dependent hemostasis. These findings reveal that EVs from senescent endothelial cells contribute to platelet activation, a process that may favor thrombosis in patients receiving Doxorubicin-based chemotherapy.