Wednesday, January 23, 2013

ANGIOGENESIS


ANGIOGENESIS

Angiogenesis is the growth of new blood vessels from pre-
     existing vessels.
-    occurs in the healthy body for healing wounds and for
     restoring blood flow to tissues after injury; in females, to
     rebuild the uterus lining, and during pregnancy to build the
     placenta
  - also a fundamental step in the transition of tumors from a
    dormant state to a malignant one

Facts & Figures
    * The total surface area covered by these cells in an adult is
1000-- roughly the size of a tennis court.
   * If all the blood vessels in the body were lined up end-to-
      end, they would form a line that could circle the earth twice.
   * Blood vessel cells do not normally grow in the healthy adult
      they are normally inactive, or quiescent.

 

 Two Types of Angiogenesis:

1. Sprouting angiogenesis - vessel formation & growth as
     entirely new vessels; involves mural/pericytes & smooth
     muscle cells
2. Intussusceptive/ splitting angiogenesis - the capillary wall
    extends into the lumen to split a single vessel in two.

Vasculogenesis (spontaneous blood vessel formation) is
    the process of blood vessel formation occurring by a de
    novo production of endothelial cells; when endothelial
    precursor cells (angioblasts –endothelial cells)
    & smooth muscles (from myofibroblasts) migrate and
    differentiate in response to local cues (such as growth
    factors and extracellular matrix) to form new blood vessels.

Arteriogenesis is the formation of medium-sized blood
     vessels possessing tunica media & adventitia.
     - also involves increase in the diameter of existing
        arterial vessels.
     - common response to physical exercise &
       atherosclerosis

Origin: intermediate mesoderm, lateral plate mesoderm

Terms:
* endothelial cells –line the interior surface of blood
      vessels &  lymphatic vessels,
* pericytes/Rouget’s/mural cells –contractile cells that wrap
      around the endothelial cells of capillaries and venules
* angioblasts – endothelial progenitor cells; one of the two
       products formed from hemangioblasts (the other being

Control:
The healthy body controls angiogenesis through a series of "on" and "off" switches:
  • The main "on" switches are known as angiogenesis-stimulating growth factors
  • The main "off switches" are known as angiogenesis inhibitors
The normal, healthy body maintains a perfect balance of angiogenesis modulators. In general, angiogenesis is "turned off" by the production of more inhibitors than stimulators.

Chemical Signals:
Angiogenic Growth Factors
* Fibroblast Growth Factor (FGF) – initiate a process of
      mitogenic activity critical for the growth of endothelial cells,
      fibroblasts, and smooth muscle cells.
      - promotes healing in chronic wounds of DM patients
* vascular endothelial growth factors (VEGFs) – increase the
      number of capillaries in a given network
*  at least 20 other GFs
Angiogenic Inhibitors:
* Angioarrestin – to inhibit proliferation induced by VEGF of
      vascular endothelial cells derived from different vessel type
* Angiostatin (plasminogen fragment) – involve inhibition of
     endothelial cell migration, proliferation and induction of
     apoptosis
* at least 30 (300 to date) other angiogenic inhibitors
  
Excessive angiogenesis:
     *  in cancer, diabetic blindness, age-related macular
       degeneration, rheumatoid arthritis, psoriasis, and more
       than 70 other conditions.
       - diseased cells produce abnormal amounts of angiogenic
         GFs, overwhelming the effects of angiogenesis inhibitors.
  • Anti-angiogenic therapies – starve diseased cells

Insufficient angiogenesis:
      * in coronary artery disease, stroke, ischemic heart
        disease, and chronic wounds
       - cannot produce adequate amounts of angiogenic GFs
·         Therapeutic angiogenesis to stimulate angiogenesis,
 improve perfusion, deliver survival factors to sites of
tissue repair, mobilize regenerative stem cell
populations, and ultimately, restore form and function
-  possibly for regeneration of nerves