1. Endocrine
   1. Contribute to the formation and maintenance of extracellular matrix
   2. Produce growth factors in response to damage.
      1. colony stimulating factors
   3. Secrete substances that regulate platelet clumping, clotting, and anticlotting.
   4. Synthesize active hormones from inactive precursors
   5. Extract or degrade hormones and other mediators
   6. Secrete cytokines during immune responses
   7. Mediate angiogenesis
      1. by a variety of angiogenic factors (eg VEGF) (also secreted by fibroblasts and other tissue cells)
2. Blood flow
3. Vascular tone
4. Vascular structure
5. Haemostasis
   1. endothelial cells secrete
      1. vWF
      2. prostacyclin (aka PGI2)
         1. inhibits platelet aggregation
      3. NO
         1. inhibitor of platelet adhesion, activation and aggregation
      4. tissue factor pathway inhibitor
      5. tissue plasminogen activator (t-PA)
   2. endothelial cells have
      1. thrombomodulin receptors
      2. heparin on surface
   3. Summary
      1. Normally provide an intact barrier between the blood
         1. Platelet aggregation and the formation of tissue factor–and subendothelial connective tissue factor VIIa complexes are not triggered
      2. Synthesize and release PGI2 and nitric oxide
         1. These inhibit platelet activation and aggregation
      3. Secrete tissue factor pathway inhibitor
         1. Inhibits the ability of tissue factor–factor VIIa complexes to generate factor Xa
      4. Bind thrombin (via thrombomodulin), which then activates Protein C
         1. Active protein C inactivates clotting factors VIIIa and Va
      5. Display heparin molecules on the surfaces of their plasma
         1. Heparin binds antithrombin III, and this molecule then membranes inactivates thrombin and several other clotting factors
      6. Secrete tissue plasminogen activator
         1. Tissue plasminogen activator catalyzes the formation of plasmin, which dissolves clots
6. Lipid metabolism
   1. fatty acids of plasma chylomicrons are released, mainly within adipose- tissue capillaries, by the action of endothelial lipoprotein lipase
7. Paracrine
   1. Nitric Oxide
      1. what influences their release
         1. Shear stress
         2. Acetylcholine
         3. VIP
         4. Products of platelet aggregation
         5. (adenine and adenosine nucleotides)
         6. Bradykinin
         7. Histamine
         8. ADP
            1. (adenine and adenosine nucleotides)
         9. Substance P
         10. serotonin
      2. actions
         1. Vasodilator
      3. mechanism of action
         1. ADP
            1. (adenine and adenosine nucleotides)
         2. Bradykinin
         3. Histamine
         4. Substance P
         5. serotonin
         6. shear stress
            1. shear force induced deformation of the endothelial cell cytoskeleton
            2. activation of enzymes
            3. PI3K
            4. Akt
            5. stimulates NOS via phosphorylation
         7. After NO is synthesised...
            1. diffuse through vascular wall into smooth muscle cells
            2. activates guanylyl cyclase
            3. which increases levels of cellular cyclic GMP
            4. which causes relaxation
         8. via
            1. initiation and sustained release of CALCIUM from endoplasmic reticulum and calcium channels respectively.
            2. calmodulin complex: Nitric Oxide Synthase
            3. converts L-arginine and Oxygen into Nitric Oxide
      4. Etc
         1. NO = free radical
            1. reacts very rapidly with superoxide
            2. and forms peroxynitrite
            3. THEREFORE: NO survives for only a few seconds
            4. effects of NO exerted locally
            5. effect depends on its continual production
   2. Angiotensin II
      1. ACE produces vasoconstrictor angiotensin II and breaks down vasodilator bradykinin
   3. EDHF (Endothelium derived hyperpolarising factor)
      1. what influences their release
      2. actions
         1. dilatation of arterioles
         2. smooth muscle hyperpolarisationn
      3. mechanism of action
         1. endothelial hyperpolarisation
            1. directly transmitted to surrounding smooth muscle cells
            2. through myoendothelial gap junctions which connnect these two types of cells and allow current to flow between them
   4. Endothelin
      1. what influences their release
         1. angiotensin II
         2. thrombin
         3. vasopressin
         4. epinephrine
      2. actions
         1. vasoconstrictor
      3. mechanism of action
         1. stimulates receptors on vascular smooth muscle cells (ET-A and ET-B)
            1. stimulates G-Protein-linked mechanisms
            2. Calcium influx, release, sensitisation
   5. Prostanoids
      1. Thromboxane-A2/Prostaglanding H2
         1. what influences their release
            1. angiotensin II
            2. thrombin
            3. vasopressin
            4. epinephrine
         2. actions
            1. vasoconstrictors
      2. Prostacyclin
         1. what influences their release
            1. increasing smooth muscle cell cyclic AMP
         2. actions
            1. vasodilatation
            2. limiting platelet attachment and aggregation
8. Dysfunction
   1. Cause
      1. Hyperlipidaemia
      2. Hypertension
      3. Hyperhomocysteinemia
      4. Menopause
      5. Aging
      6. Poor diet
      7. Cigarette smoking
      8. Diabetes
   2. Effects
      1. Less NO
      2. More ET-1