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Dermatology
Vascular Biology
Built from Dermatology, 5th Edition
What’s inside
10 sections · 95 slides
Overview
- What this topic covers
- Key features
- Roles of the cutaneous vascular system
Cutaneous Blood Vessels
How the skin's blood supply is built, from large arteries down to capillary loops
- Two layers of blood supply
- Layout of the cutaneous vascular system
- Capillary loops vary by body site
- Perfused skin vessels form an irregular mesh
- Blood vessels and lymphatics stain differently
- Blood supply of the hair follicle
- Vascular mesh around a growing hair follicle
- Regulating body temperature and pressure
- One-way valves in small veins
- The blood vessel wall
- Weibel-Palade bodies: storage granules
- Other ultrastructural features
- Telling blood vessels from lymphatics
- Immunohistochemical markers for blood vessels and lymphatics
- Distinguishing blood vessels from lymphatics by double staining
- A second example: separate blood and lymphatic staining
Vascular Development
How the first blood vessels form in the embryo, and how new ones sprout later in life
- Vasculogenesis: building the first vessels
- From hemangioblast to mature vessel
- Steps from precursor cell to mature blood vessel
- Angiogenesis: sprouting new vessels
- Notch signaling picks the leader
- How the leading tip cell is selected
- Angiopoietins keep vessels stable -- or not
- Angiopoietins switch a vessel between quiet and growing states
- Other signals that shape new vessels
Regulating Skin Angiogenesis
Adult skin vessels sit quiet most of the time -- what switches angiogenesis on
- Adult skin vessels are usually quiet
- Angiogenesis starts with a leaky vessel
- The stepwise induction of angiogenesis
- Leaky vessels build a scaffold for growth
- Pericytes: the brakes on angiogenesis
- Clearing the basement membrane
- VEGF-A: the master angiogenesis signal
- How VEGF-A and PlGF signal from the epidermis to blood vessels
- VEGF-A rises in disease, not healthy skin
- Epidermal growth links to new vessel growth
- Evidence from mouse models
- Placental growth factor (PlGF)
- Thrombospondin: the body's brake pedal
- The thrombospondin family of matricellular proteins
- TSP-2 and other natural inhibitors
Angiogenesis in Wound Healing
New capillaries feed the tissue that rebuilds a wound
- New vessels build the wound's scaffold tissue
- What triggers vessel growth in a wound
- Signals that drive and later restrain wound angiogenesis
- Vessel growth then pulls back
- Stabilizing the new network
Leukocytes and the Vessel Wall
How white blood cells leave the bloodstream and enter inflamed skin
- Leukocytes must exit through the vessel wall
- Four steps out of the bloodstream
- Leukocyte-endothelial cell interactions, step by step
- Selectins start the process
- From rolling to a firm grip
- Major adhesion molecules in leukocyte-endothelial cell interactions
- Major adhesion molecules in leukocyte-endothelial cell interactions (continued)
- Structure of the selectin and immunoglobulin adhesion families
- Squeezing through the vessel wall
Cutaneous Lymphatic Vessels
A second vessel network that drains fluid and carries immune cells
- What lymphatic vessels do
- A looser wall than blood vessels
- Two lymphatic layers, like the blood supply
- Sensing and draining extra fluid
- Lymphatic capillaries widen to drain excess tissue fluid
- How lymphatic vessels develop
- Steps in embryonic lymphatic vessel development
- Markers unique to lymphatic vessels
- Podoplanin keeps blood out of lymphatics
- LYVE-1: a hyaluronic acid receptor
- VEGF-C and VEGF-D grow lymphatics
- Growth factors and receptors that build blood versus lymphatic vessels
- Other lymphangiogenesis signals
Vascular and Lymphatic Disease
What happens when these growth signals go wrong
- Angiogenesis-driven skin diseases
- Genetic vascular malformations
- Lymphedema: when drainage fails
- Other inherited lymphatic gene defects
- Angiogenesis failure: diabetic wounds
- Lymphatic vessels and cancer spread
Antiangiogenic Therapies
Drugs that starve tumors, and other vessel-targeted treatments
- Why block angiogenesis in cancer
- Ways drugs can block the VEGF-A / VEGFR-2 pathway
- Bevacizumab and related antibodies
- Small-molecule tyrosine kinase inhibitors
- Why anti-VEGF drugs sometimes stop working
- Combining therapies for better results
- Vessel-targeted therapy beyond cancer
- Antiangiogenic therapy in eye disease
Putting It Together
The big ideas to carry forward from cutaneous vascular biology
- Two networks, two jobs
- VEGF is the common thread
- Balance, not just growth
- References
- References (continued 2/7)
- References (continued 3/7)
- References (continued 4/7)
- References (continued 5/7)
- References (continued 6/7)
- References (continued 7/7)
- Dermatology, 5th Edition (2-Volume Set)