The Relationship Between Blood Cells and Vascular Endothelial Cells
Blood cells interact with vascular endothelial cells through multiple critical mechanisms including adhesion molecule expression, glycocalyx-mediated regulation, extracellular vesicle signaling, and coagulation pathway activation, forming an integrated system essential for vascular homeostasis and disease pathogenesis. 1
The Neurovascular Unit Concept
The relationship between blood cells and vascular endothelium must be understood within the framework of the "neurovascular unit," which recognizes that vascular endothelial cells, blood cells, and surrounding tissues (neurons, glia, smooth muscle cells, pericytes) function as a developmentally, structurally, and functionally integrated system rather than isolated components 1, 2. This conceptual framework is critical because it emphasizes that endothelial-blood cell interactions cannot be separated from their broader tissue context 1.
Direct Blood Cell-Endothelial Interactions
Adhesion Molecule-Mediated Communication
Vascular endothelial cells actively participate in thromboinflammation by expressing adhesion molecules that facilitate direct interactions with leukocytes and platelets, creating procoagulant, proadhesive, and proinflammatory conditions that enable microthrombus formation. 1
- Endothelial cells upregulate adhesion molecules (including ICAM-1) in response to inflammatory stimuli like TNF-α, which directly recruit and bind circulating leukocytes 1
- This adhesion molecule expression represents a critical mechanism by which endothelial cells transition from an anti-thrombotic to a pro-thrombotic phenotype during disease states 1
Glycocalyx as a Regulatory Interface
The endothelial glycocalyx serves as a gel-like barrier covering the vascular lumen that exhibits antithrombotic, anti-inflammatory, and vascular permeability regulatory functions, directly modulating blood cell interactions with the endothelial surface 1.
- When degraded by inflammatory mediators (heparanase, matrix metalloproteases, reactive oxygen species, thrombin, elastase), circulating glycocalyx components (syndecans, hyaluronic acid, heparan sulfate) serve as biomarkers of endothelial injury 1
- Glycocalyx shedding exposes the endothelial surface to direct blood cell contact, fundamentally altering the blood-endothelium relationship 1
Extracellular Vesicle-Mediated Signaling
Endothelial cells release extracellular vesicles (0.03 to 5.00 μm diameter) that act as mediators between endothelial cells and blood cells, with activated endothelial cells propagating procoagulant activity through enhanced release of phosphatidylserine-expressing vesicles. 1
- Endothelial-derived extracellular vesicles activate neutrophil oxidative function and stimulate coagulation in sepsis, demonstrating bidirectional communication 1
- These vesicles contain miRNAs (including miR-146a) that promote angiogenesis and regulate vascular responses 1
- Platelet-derived extracellular vesicles reciprocally interact with endothelial cells, mediating atherogenic interactions and regulating coagulation responses 1
Hemocompatibility and Blood Cell Survival
Vascular endothelial cells represent the prototypic hemocompatible interface because they express blood regulatory molecules that keep innate immune cascades in check, preventing inappropriate activation of circulating blood cells. 1
- Endothelial cells maintain an antithrombotic surface under physiological conditions, contrasting with extravascular cells (smooth muscle cells, fibroblasts) that express tissue factor and other procoagulant molecules 1
- This hemocompatibility is essential for preventing instant blood-mediated inflammatory reactions (IBMIR) that would otherwise compromise vascular integrity 1
Pathophysiological Implications
Endothelial Dysfunction as a Disease Mechanism
Endothelial dysfunction represents a hallmark of human diseases including peripheral vascular disease, stroke, heart disease, diabetes, chronic kidney failure, and venous thrombosis, with compromised endothelial function directly contributing to disease progression and predicting cardiovascular events. 3, 4
- Atherogenic stimuli (diabetes, dyslipidemia, oxidative stress) induce vascular dysfunction through endothelial cell alterations, leading to atherosclerosis 5
- Reactive oxygen species generation and reduced nitric oxide production by endothelial cells impairs blood vessel function and alters blood cell interactions 6
Blood-Brain Barrier Dysfunction
Blood-brain barrier dysfunction plays a pivotal role in cerebral small vessel disease development, with disruption of the neurovascular unit (neurons, glia, vascular cells) contributing to disease progression and vascular cognitive impairment 2. This represents a specialized example of how endothelial-blood cell relationships affect organ-specific pathology 2.
Rheological Considerations
Physical forces imposed by flowing blood, particularly shear stress and blood viscosity, determine endothelial function through mechanotransduction pathways, with cell-cell interactions and reactive oxygen species playing central roles in both physiological and pathological states. 7
Clinical Biomarkers of Endothelial-Blood Cell Dysfunction
The International Society on Thrombosis and Haemostasis recognizes that endothelial dysfunction markers can improve early detection and outcome prediction in disseminated intravascular coagulation, though current diagnostic criteria focus primarily on coagulation parameters rather than endothelial markers 1. Key accessible biomarkers include:
- Soluble thrombomodulin (cleaved from endothelial surface) 1
- Plasminogen activator inhibitor-1 (PAI-1) levels reflecting endothelial fibrinolytic dysfunction 1
- Angiopoietin-2 levels indicating endothelial activation 1
- von Willebrand factor as a marker of endothelial perturbation 1
Common pitfall: Current clinical practice often overlooks endothelial dysfunction markers in favor of traditional coagulation parameters, potentially missing early disease detection opportunities 1.