Role of exosomes and microvesicles in hypoxia-associated tumour development and cardiovascular disease.

Exosomes and microvesicles, collectively referred to as extracellular vesicles (EVs), can transfer complex biological information and induce a diverse signalling response in recipient cells with potential relevance in a wide array of pathological conditions. Tissue hypoxia constitutes a stress-associated phenotype that is central to the malignant state of aggressive tumours as well as to ischaemic tissue in cardiovascular disorders. The adaptive response to hypoxic stress is largely dependent on intercellular communication in which EVs, and cellular exchange of EV cargo molecules, have recently been implicated. The results of numerous studies indicate that hypoxia-dependent shaping of the molecular profile of EVs may mediate the biological response to hypoxia. EVs have been shown to induce tumour angiogenesis and hypercoagulation as well as tissue remodelling and protective effects in ischaemic cardiovascular conditions. Recent findings report increased levels of circulating EVs in patients with hypoxia-associated disorders such as myocardial infarction, stroke and pre-eclampsia, indicating a role of EVs as biomarkers in these pathophysiological states. Here, we discuss the intriguing role of EVs in tumour development and cardiovascular disease, focusing on the paracrine transfer of the hypoxic response to neighbouring cells and to distant cells at the systemic level, with wide implications for biomarker discovery and therapeutic intervention.