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Structure and Function of Blood Vessels Peter Takizawa Department of Cell Biology

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Page 1: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Structure and Function of Blood Vessels

Peter TakizawaDepartment of Cell Biology

Page 2: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

What we’ll talk about…

• Structure of blood vessels and their appearance in histological samples

• Endothelium and structures that control permeability

• Increasing endothelial permeability and leukocyte transmigration

• Smooth muscle and vascular repair

• Angiogenesis

Page 3: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Blood vessels comprise three functional layers.

Page 4: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Endothelial cells perform a variety of structural and biochemical functions.

• Permeability

• Immune response

• Angiogenesis

• Modulate vascular resistance

• Antihaemostatic and haemostatic control

• Enzymatic action on plasma proteins

Page 5: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

The aorta is an elastic artery that contains numerous elastic fibers in the media.

MediaAdventitiaIntima

Smooth Muscle Cell

Elastic Fiber

Internal Elastic Lamina

Vasa Vasorum

Endothelial Cell

Page 6: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Muscular arteries contain more smooth muscle and fewer elastic fibers in the media layer.

MediaAdventitia

Intima

Internal Elastic Lamina

Endothelial Cell

External Elastic Lamina

Smooth Muscle Cell

Page 7: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Small muscular arteries contain fewer layers of smooth muscle.

Endothelial Cell

Smooth Muscle Cell

Page 8: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Arterioles control blood flow into capillaries and create the highest resistance in the circulatory system.

Endothelial Cell

Smooth Muscle Cell

Page 9: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Arterioles have one or two layers of smooth muscle cells.

Endothelial Cell

Smooth Muscle Cell

Page 10: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Capillaries contain a single layer of endothelial cells and the occasional pericyte.

Endothelial Cell Capillary Lumen

Pericyte

Page 11: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Permeability of capillaries

Page 12: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Small molecules and ions diffuse across capillaries but proteins are restricted in most capillaries.

s

Sugars

Small Protein Large Protein

Page 13: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Capillaries restrict the diffusion of protein to maintain oncotic pressure.

Protein Protein

Page 14: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Primary components that regulate permeability of capillaries.

• Structure of endothelial cells

• Basement membrane

• Intercellular junctions between endothelial cells

• Glycocalyx

Page 15: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Structure of Endothelial Cells

Page 16: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Continuous capillaries contain endothelial cells that only allow passage through intercellular junctions.

Endothelial Cell

Intercellular Junctions

Pericyte

Page 17: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Fenestrated capillaries have endothelial cells with several gaps for diffusion of solutes.

Endothelial Cell

Fenestrae

Pericyte

Page 18: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Discontinuous capillaries contain large pores and lack a basement membrane.

Endothelial Cell

FenestraeLumen

Page 19: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Basement membrane is a negatively-charged barrier on the basal surface of endothelial cells.

Basement Membrane

Red Blood Cell

Endothelial Cell

Page 20: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Junctional complexes restrict paracellular diffusion between endothelial cells.

Lumen

Lumen

Interstium

Page 21: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Glycocalyx restricts diffusion of large, negatively charged molecules.

Glycocalyx Glycocalyx Removed

Page 22: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Transcytosis of Proteins

Page 23: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Receptor-mediated endocytosis transports specific proteins across endothelium via transcytosis.

Blood

Interstitium

Page 24: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Transcytosis mediates movement of proteins across endothelial cells.

Lumen

Lumen

Endocytic Vesicle

Endocytic Vesicle

Interstitium

Release of Material

Release of Material

Intercellular Junction

Interstitium

Page 25: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Increasing the Permeability of Blood Vessels

Page 26: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Inflammatory molecules and immune cells activate signaling pathways that disrupt junctions.

Kinases

Myosin

Disrupt Junctions

Increase Tension

Modify Cadherins

Page 27: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Thrombin increase vascular permeability through tension on adhesion junctions.

Page 28: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Immune cells must pass across endothelial cells to reach sites of infection.

Page 29: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Rolling Adhesion Emigration

Timothy Springer Lab, Harvard Medical School

Leukocyte transmigration consist of three distinct steps.

Page 30: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Selectins and integrins mediate rolling and adhesion of immune cells.

Capture Rolling Arrest Transmigration

Selectins Integrins

Page 31: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Leukocytes disrupt adhesion junctions to migrate across endothelium.

Page 32: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Venules and Veins

Page 33: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Venules have an endothelium and relatively thin layer of smooth muscle.

Endothelial Cell

Smooth Muscle Cell

Page 34: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Venules have thinner medial layers than arteries and tend to lose their shape.

Endothelial Cell Smooth Muscle Cell

Artery

Venule

Page 35: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

The vena cava has a thinner media than the aorta with mostly smooth muscle cells and collagen.

Smooth Muscle Cell

Intima

Media

Adventitia

Page 36: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Lymphatic vessels have thin walls and lack red blood cells.

Endothelial Cell

Lymphatic Vessel

Venule

Arteriole

Page 37: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Vascular Repair

Page 38: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Damage recruits smooth muscle cell progenitors to the intima.

Damage

Endothelial Cell

Smooth Muscle Cell

Page 39: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Smooth muscle proliferation can lead to occlusion of arteries after insertion of stents.

Page 40: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Angiogenesis

Page 41: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

VEGF triggers morphological changes in endothelial tip cells.

High O2 Low O2

Page 42: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Tip cells follow guidance cues to connect to existing vessels.

Semaphorins

Page 43: Structure and Function of Blood Vessels - Yale Universitytbl.med.yale.edu/files/structure_and_function_of_blood... · 2020. 9. 7. · Basement membrane is a negatively-charged barrier

Tumor cells initiate angiogenesis to increase their blood supply.

VEGF VEGF

Tumor cells Stromal cells