The vascular endothelium is a vital component in maintaining the structure and function of blood vessels. The endothelial cells (ECs) mediate vital regulatory functions such as the proliferation of cells, permeability of various tissue membranes, and exchange of gases, thrombolysis, blood flow, and homeostasis. The vascular endothelium also regulates inflammation and immune cell trafficking, and ECs serve as a replicative niche for many bacterial, viral, and protozoan infectious diseases. Endothelial dysfunction can lead to vasodilation and pro-inflammation, which are the hallmarks of many severe diseases. Exosomes are nanoscale membrane-bound vesicles that emerge from cells and serve as important extracellular components, which facilitate communication between cells and maintain homeostasis during normal and pathophysiological states. Exosomes are also involved in gene transfer, inflammation and antigen presentation, and mediation of the immune response during pathogenic states. Protozoa are a diverse group of unicellular organisms that cause many infectious diseases in humans. In this regard, it is becoming increasingly evident that many protozoan parasites (such as Plasmodium, Trypanosoma, Leishmania, and Toxoplasma) utilize exosomes for the transfer of their virulence factors and effector molecules into the host cells, which manipulate the host gene expression, immune responses, and other biological activities to establish and modulate infection. In this review, we discuss the role of the vascular endothelium and exosomes in and their contribution to pathogenesis in malaria, African sleeping sickness, Chagas disease, and leishmaniasis and toxoplasmosis with an emphasis on their actions on the innate and adaptive immune mechanisms of resistance.

Endothelial cell-derived extracellular vesicles are produced by both activated and apoptotic endothelial cells, and play a pivotal role in various physiological conditions such as inflammation, repair, programmed cell death, and immune responses. There is a large body of evidence on the dysregulation of synthesis and secretion of several types of endothelial cell-derived extracellular vesicles, which can then trigger microvascular inflammation, atherosclerotic plaque formation, plaque rupture, thrombosis and endothelial dysfunction. The development of atherosclerosis and cardiovascular events is associated with an increased number of apoptotic, endothelial cell-derived vesicles and a decrease in activated, endothelial cell-derived vesicles. This review depicts the role of endothelial cell-derived extracellular vesicles in the manifestation and progression of atherosclerosis. We also discuss the clinical use and benefits of altering the immune phenotypes of extracellular vesicles originating from endothelial cells, to function as predictive biomarkers in both asymptomatic and subclinical atherosclerosis.

Malaria infections due to the Plasmodium parasite remains a major global health problem. Plasmodium falciparum is responsible for majority of the severe cases, resulting in more than 400,000 deaths per annum. Extracellular vesicles (EVs) released by vascular cells, including parasitised erythrocytes, have been detected with increased levels in patients with malaria. EVs are thought to be involved in the pathogenesis of severe malaria, particularly cerebral malaria, and represent a unique molecular signature for different forms of the infection. In this review, we will cover the known effects of EVs on the vasculature and discuss their potential use as a biomarker of disease severity.

The tumour vasculature plays an important role in tumour growth and metastasis. Tumour angiogenesis provides more oxygen and nutrients to growing tumour cells, is not as tightly regulated as embryonic angiogenesis, and do not follow any hierarchically ordered pattern. The heterogeneity of the vasculature, high interstitial fluid pressure, poor extravasation due to sluggish blood flow, and larger distances between exchange vessels are potential barriers to the delivery of therapeutic agents to tumours. The prevention of angiogenesis, normalization of tumour vasculature, and enhancement of blood perfusion through the use of monoclonal antibodies against receptor proteins that are overexpressed on proangiogenic tumour cells, and improved, tumour-targeted delivery of therapeutic agents can all be achieved using nanocarriers of appropriate size. Nanomedicines such as polymeric nanoparticles, lipid nanoparticles, micelles, mesoporous silica particles, metal nanoparticles, noisomes, and liposomes have been developed for the delivery of anticancer drugs in combination with antiangiogenic agents. Amongst them, liposomal delivery systems are mostly approved by the FDA for clinical use. In this review, the molecular pathways of tumour angiogenesis, the physiology of tumour vasculature, barriers to tumour-targeted delivery of therapeutic agents, and the different strategies to overcome these barriers are discussed.

Pulmonary hypertension is a serious disorder with a high morbidity and mortality rate. The juxtaposition of endothelial cells and smooth muscle cells maintains vascular homeostasis. Vascular injury results in endothelial dysfunction, leading to impaired vascular relaxation, cell proliferation, and altered immune and metabolic states. In addition, injury induces pulmonary arterial endothelium and other cells to release increased levels of extracellular vesicles, including exosomes and microparticles that may be involved in enhancing the proliferation of apoptosis-resistant smooth muscle cells. These extracellular vesicles carry proteins, lipids, RNA, miRNA, chemokines cytokines and modulate immune function, inflammation, embryogenesis, regenerative processes, and serve as intercellular messengers. Importantly, mesenchymal stem cells-derived extracellular vesicles exert inhibitory effects on inflammation and restore homeostasis. This article reviews the pathophysiological role of extracellular vesicles in pulmonary hypertension.

The role of exosomes in different physiological and pathological settings is an emerging field of great current interest. One hallmark of exosomes is the promotion of blood vessel formation. Exosomes of different cellular origin have been shown to be enriched in angiogenic proteins which directly promote angiogenesis. In addition, exosomes are also efficacious producers of adenosine and potentially encapsulate adenosine in their lumen. The adenosine content of exosomes has been linked to their immunosuppressive effects. In this communication, we consider the possibility that adenosine production by tumor cell-derived exosomes may represent a novel pathway for stimulation of angiogenesis in the tumor microenvironment.