Endothelial Cells - In Depth Notes

  • Endothelium:

    • Inner layer of all blood vessels and lymphatic system.

    • One cell layer thick, in contact with fluids (blood and lymph).

    • Largest organ in the body (endocrine), weighing over 1 kg in adults.

    • Composed of 1-2 trillion cells, covering 4000-7000 m² (equivalent to 8 tennis courts).

  • Structural Features of Endothelial Cells:

    • Appearance:

      • Flat, 1-2 μm thick, and 10-20 μm in diameter, resembling cobblestones.

    • Glycocalyx:

      • Composed of proteoglycans with carbohydrate chains (glycosaminoglycans).

      • Protects intercellular junctions, crucial for maintaining vessel integrity.

      • Toxic substances can disrupt these junctions, leading to diseases.

    • Tight intercellular junctions to maintain integrity of the vessel wall:

    • Toxic substances (e.g. nicotine) open up these junctions and allow large molecules to pass through the wall.

    • This can lead to disease (future lectures).

  • Cell Functions:

    • Vesicle Transport:

    • Contains many vesicles utilized for pinocytosis and macropinocytosis for solute and fluid transport.

    • Caveolae: Special type of vesicle that contains caveolin, associated with various cellular functions.

  • Endothelial Cell Roles:

    1. Vascular Tone Management:

    • Responds to hormones and vasoactive factors, controlling dilation and constriction.

    • Vasodilatory Factors:

      • Nitric Oxide (NO), Prostacyclin (PGI2), Endothelium-derived Hyperpolarizing Factor (EDHF).

    • Vasoconstrictive Factors:

      • Thromboxane A2 (TXA2), Endothelin-1 (ET-1), Catecholamines.

    1. Coagulation and Thrombosis Regulation:

    • Produces both activators and inhibitors of thrombus formation:

      • Anticoagulants: Thrombomodulin, Protein C, TFPI.

      • Produces factors to inhibit platelet function: NO, PGI2.

    1. Inflammation Regulation:

    • ECs interact with leukocytes, enabling attachment, rolling, and transmigration during inflammation.

    • Mechanism:

      • Tethering (selectins), slow rolling/arrest (integrins).

  • Mechanical Forces on Endothelial Cells:

    • ECs experience various forces:

    • Contact-Derived Stresses: Influence of topography and curvature, stiffness (2 kPa - 2 MPa).

    • Flow-Derived Stresses: Shear stress (0.1-5 Pa), pressure variations in arteries (120/80 mmHg).

  • Mechanosensation in Endothelial Cells:

    • Cells utilize several mechanisms for sensing their environment:

    • Glycocalyx, ECM via integrins, tight junction proteins, and ion channels.

    • Shear stress induces conformational changes, activating signaling pathways, and affecting gene transcription.

  • Endothelial Dysfunction:

    • Causes: Oxidative stress, inflammation, and various risk factors (hypercholesterolemia, diabetes, etc.).

    • Leads to impaired endothelial function contributing to diseases such as atherothrombosis, myocardial infarction, and stroke.

    • Symptoms of Dysfunction: Decreased NO signaling, increased inflammation and permeability, and vascular stiffness.

  • Summary of Key Points:

    • ECs maintain cardiovascular health through multiple mechanisms including regulating vascular tone, preventing thrombosis, and managing inflammatory responses.

    • Mechanical and biological factors influence their functionality and overall health.

  • Assessment Question Example:

    • Question: Describe 1 biological and 1 mechanical mechanism by which the glycocalyx has a signalling role on endothelial cells.

    • Biological Mechanism: Glycocalyx sequesters growth factors which modulate receptor accessibility that leads to intracellular signaling.

    • Mechanical Mechanism: Structural changes in glycocalyx components leading to cytoskeletal rearrangement via integrin interactions.

  • Next Lecture:

    • Focus: Smooth Muscle Cells