Chronic inflammation and Angiogenesis

Chronic inflammation and Angiogenesis

These are two closely related processes.

Angiogenesis is the growth of new blood vessels from existing ones.

Inflammation brings growth chemicals to stimulate healing.

  They are both complex processes and an important aspect of new tissue development, tissue growth, and tissue repair.  So, it only makes sense that we now find there is considerable evidence to suggest that angiogenesis and chronic inflammation are co-dependent.

      Dr. Li says it is also significant that inflammatory cells may amplify the angiogenic switch!Angiogenesis is normally a tightly controlled process.  However, cancer is associated with aberrant angiogenesis. There has long been evidence suggesting that these are two closely related processes.

A Bit of “Clinic-ese”  

   Angiogenesis supports inflammation by leukocyte migration, cellular infiltration, growth factors and cytokines. We have begun to understand the codependence of chronic inflammation and angiogenesis and of targeting chronic inflammation to affect angiogenesis. (1)

   Inflammation releases a variety of angiogenic factors that initiate angiogenesis.  The processes are distinct and separable but there is growing evidence that the angiogenesis accompanies chronic inflammation. These findings have even led to the proposed use of anti-angiogenesis drugs in the treatment of IBD. (2-3)

   The balance between angiogenic and angiostatic factors determines the existence and rate of blood vessel proliferation in a tissue. In inflammation, this balance is clearly tipped in favor of angiogenesis. Inflammation is also associated with the recruitment of leukocytes, platelets, macrophages, mast cells, and fibroblasts – all of which can produce pro-angiogenic factors, including VEGF and cytokines. (4-5)

   Collectively, these responses appear to be geared toward enhancing the delivery of inflammatory cells to the injured/infected tissue, isolating the region from healthy tissue and the systemic circulation, and setting the stage for tissue repair and regeneration. (6-7)

   It appears that virtually every cell in or through the inflamed region is activated.  This allows the cells that have a stake in the outcome of the inflammatory response to make a meaningful contribution. The cells respond in much the same way – by producing ROS or releasing cytokines and/or proteases. (8)

What It All Means

   We have seen, from other articles, that cancer prevention and treatment should involve preventing or removing the blood supply to them.  With no blood, they can’t grow!

   We are also now seeing that inflammation works with and encouraged blood vessel growth (angiogenesis). So, if we want to prevent cancer tumors from building a blood supply,

We may also want to
reduce chronic inflammation!

   Since one feeds the other, a good cancer preventative and protocol should include nutrients that would help reduce inflammation.  Thus, we have added our recommended inflammation nutrient blend to our anti-angiogenesis blend.

References

1. Jackson, Seed, Kircher, Willoughby, Winkler, The codependence of angiogenesis and chronic inflammation, The Federation of American Societies for Experimental Biology, 1997.

2. Koutroubakis IE, Tsiolakidou G, Karmiris K, Kouroumalis EA. Role of angiogenesis in inflammatory bowel disease. Inflamm Bowel Dis. 2006; 12: 515–23.

3. Naldini A, Carraro F. Role of inflammatory mediators in angiogenesis. Curr Drug Targets Inflamm Allergy. 2005; 4: 3–8.

4. Lingen MW. Role of leukocytes and endothelial cells in the development of angiogenesis in inflammation and wound healing. Arch Pathol Lab Med. 2001; 125: 67–71.
5. Arenberg DA, Strieter RM. Angiogenesis. In Inflammation: Basic Principles and Clinical Correlates (pp. 851–864), 3rd edition edited by John I. Gallin and Ralph Snyderman. Lippincott Williams & Wilkins, Philadelphia, 1991.

6. Majno G. Chronic inflammation: links with angiogenesis and wound healing. Am J Pathol. 1998; 153: 1035–39.

7. Shibuya M. Brain angiogenesis in developmental and pathological processes: therapeutic aspects of vascular endothelial growth factor. FEBS J. 2009; 276: 4636–43.

8. Nagy JA, Benjamin L, Zeng H, Dvorak AM, Dvorak HF. Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis. 2008; 11: 109–19.

Additional Reference:

Flister MJ, Wilber A, Hall KL, Iwata C, Miyazono K, Nisato RE, Pepper MS, Zawieja DC, Ran S. Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-kappaB and Prox1. Blood. 2010; 115: 418–29.