Angiogenesis and Shark Cartilage

A report on angiogenesis and psoriasis, along with notes about shark-cartilage products.

Angiogenesis is the process by which new blood vessels are grown in a person’s body. Once a person is an adult, angiogenesis shuts off, for the most part, except for during parts of a woman’s reproductive cycle and when wounds need to be healed. As part of the latter, cells in the skin are readily able to induce angiogensis to form new capillaries, and it is widely recognized that in many inflammatory conditions, they do just that. Angiogenesis also occurs in the formation of tumors, and many anti-angiogenic substances have been tested to combat cancer. A few of them, like shark cartilage, have also been tested to see if they can treat psoriasis.

It has been known that angiogenesis occurs in psoriasis for many years.[1-8] It appears that only one published report has ever disputed this[9], and that seems to have been largely ignored. Angiogenesis has also been reported to occur in psoriatic arthritis[10-12], and again only one report seems to contradict this[13], but it appears that those researchers were looking for similarities to cancer, instead of angiogenesis in general.

Not only is the idea that angiogenesis occurs in psoriasis well-supported, but at least two studies have found the location of the source of angiogenic factors.[14,15] Perhaps surprisingly, it turns out to be cells within the epidermis, and not the highly vascular dermis itself, which initiate the process in psoriasis. There are even different kinds of angiogenesis going on in psoriatic skin[16,17], but when combined with dilation of the capillaries, it all boils down to bright-red inflamed skin.

There is no shortage of potential inducers of angiogenesis in psoriatic skin, most readily manufactured by skin cells (this list is not necessarily complete):

· Platelet-derived endothelial cell growth factor/thymidine phosphorylase[18]

· Nerve growth factor[19]

· Scatter factor[20]

· Transforming growth factor-alpha[21,22]

· Peripheral blood mononuclear cells[23]

· Matrix metalloproteinases (MMPs)[24]

· Endothelial cell stimulating angiogenesis factor (ESAF)[25]

· Vascular permeability factor/vascular endothelial growth factor (VEGF)[25-28]

The last, VEGF, is probably the most widely-researched angiogenic molecule, as far as psoriasis research goes, but the one report I found of a search for a genetic link to the angiogenesis part of psoriasis focused on MMPs.[29]

And even though psoriasis includes angiogenesis, it appears to be just another symptom, rather than a causative factor. In other words, the psoriasis doesn’t appear because of run-away angiogenesis, the angiogenesis occurs because of the psoriasis.[30] And if you treat the psoriasis, the new blood vessels don’t necessarily go away.[31] (If I may speculate for a moment, perhaps the dense capillaries left over are responsible for the often-experienced hyperpigmentation — dark spots — left over after other psoriasis symptoms vanish from a patch of skin).

But, even if angiogenesis isn’t causal to psoriasis, and treating psoriasis doesn’t necessarily get rid of the “torturous” new web of capillaries, can treating the angiogenesis help reduce psoriasis symptoms overall? Various studies mention anti-angiogenic substances in relation to psoriasis — often just suggesting that these drugs may be useful for the treatment of psoriasis.[32] These include radicicol, ESAF analogues, and antisense oligonucleotides to the VEGF genes.[33-35] A report from 2001 claims that VEGF antagonists will be tested on psoriasis.[36]

Also, as has been shown by several studies, drugs known to combat psoriasis may do so, in part, due to anti-angiogenic properties. Cyclosporine and various retinoids are the most-researched.[37-43]

Finally, we come to shark cartilage. Cartilage is a tissue which has very few blood vessels. Sharks have a lot of cartilage. There was a rumor that sharks don’t get cancer, and since most tumors require a lot of angiogenesis, shark cartilage is sold with the idea that it can prevent the angiogenesis required for tumors to grow. However, sharks do get cancer, and there’s no particular reason to think that shark cartilage is more anti-angiogenic than, for example, cow cartilage, kitten cartilage, or even human cartilage. And if, as one web page states, sharks heal cuts and injuries very quickly, that suggests that angiogenesis works just fine for them. But I’m straying from the subject at hand.

There are two abstracts I can see which have actually tested a shark-cartilage extract on psoriasis. Both tested a compound called AE-941, also known as Neovastat. The first, a 1998 study, checked AE-941’s anti-angiogenic properties on chicken embryos, and found that it is, indeed, anti-angiogenic. The researchers also tested AE-941 topically (on the forearms) on an unknown number of test subjects, with unknown skin conditions, and found it worked as an anti-inflammatory.[44]

The second, a 2002 study, tested AE-941 orally at various doses, and found that in all but the lowest dose, it resulted in a lowered PASI score in a third to a half of 49 psoriasis patients. However, the abstract doesn’t say how much lower the PASI score got after 12 weeks. It does say that nearly 25% of the test subjects experienced “nausea, diarrhea, vomiting, flatulence, [and/or] constipation” and that four of the people got acne or a rash.[45] This study was a phase I/II study, and it will be interesting to see if the research is taken further.

Until it is, using Neovastat, even at the highest dose used in the study, is a crapshoot. And using any other kind of shark cartilage product for psoriasis would represent even more of a gamble with your money. According to IntelliHealth, “[a]t this time, there is no reliable evidence to recommend shark cartilage for psoriasis.”

Sharks may have a bad reputation, but they don’t deserve to be shamelessly exploited by quacks any more than we psoriatics do.

Web Resources for Shark Cartilage and Angiogenesis Information

Shark Cartilage Products

Please also note that children, pregnant women, and women who are attempting to conceive a child all require unhindered angiogenesis, and should not use anti-angiogenic therapies. Shark cartilage and other anti-angiogenic substances also have their own contraindications for other conditions (and medications), so read carefully before buying or using anything described above or below.

1001 Beauty Secrets

AngiobalansPDF File



Dermanex Skin Cream

Discount Vitamins & Herbs

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Herbs4goodhealth Enterprises

Mother Nature Health Products

Natural Life Shark Cartilage

The Real Life Shark Cartilage Information Exchange

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Note: I reference these papers for the information contained in their abstracts only. I am aware that the full-text articles may provide valuable additional information, but I am not able to access the full text for most of these as of this writing.

1.A critical role of placental growth factor in the induction of inflammation and edema formation.” Oura et al, Blood 2003 Jan 15;101(2):560-7

2.The angiopoietins and Tie2/Tek: adding to the complexity of cardiovascular development.” Ward and Dumont, Seminars in Cell & Developmental Biology 2002 Feb;13(1):19-27

3. “[Endothelial cells in the blood in psoriasis.]” Sochorova et al, Bratislavske Lekarske Listy 2000;101(9):529-30

4.Basement membrane alterations in psoriasis are accompanied by epidermal overexpression of MMP-2 and its inhibitor TIMP-2.” Fleischmajer et al, The Journal of Investigative Dermatology 2000 Nov;115(5):771-7

5.Vascular endothelial growth factor and the regulation of angiogenesis.” Ferrara, Recent Progress in Hormone Research 2000;55:15-35; discussion 35-6

6.New paradigms for the treatment of cancer: the role of anti- angiogenesis agents.” Cherrington et al, Advances in Cancer Research 2000;79:1-38

7.An in vivo study of the microlymphatics in psoriasis using fluorescence microlymphography.” Cliff et al, The British Journal of Dermatology 1999 Jan;140(1):61-6

8.The codependence of angiogenesis and chronic inflammation.” Jackson et al, The FASEB Journal 1997 May;11(6):457-65

9.In psoriasis the epidermis, including the subepidermal vascular plexus, grows downwards into the dermis.” Bacharach-Buhles et al, The British Journal of Dermatology 1997 Jan;136(1):97-101

10. “[Periungual capillaroscopy in psoriatic arthritis.]” Salli et al, La Clinica Terapeutica 1999 Nov-Dec;150(6):409-12

11.Angiopoietins, growth factors, and vascular morphology in early arthritis.” Fearon et al, The Journal of Rheumatology 2003 Feb;30(2):260-8

12.Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis.” Fraser et al, Arthritis and Rheumatism 2001 Sep;44(9):2024-8

13.Angiogenic factor from synovial fluid resembling that from tumours.” Brown et al, Lancet 1980 Mar 29;1(8170):682-5

14.Angiogenic properties of normal and psoriatic skin associate with epidermis, not dermis.” Malhotra et al, Laboratory Investigation 1989 Aug;61(2):162-5

15.Aberrant production of interleukin-8 and thrombospondin-1 by psoriatic keratinocytes mediates angiogenesis.” Nickoloff et al, American Journal of Pathology 1994 Apr;144(4):820-8

16.Videocapillaroscopic findings in the microcirculation of the psoriatic plaque.” De Angelis et al, Dermatology 2002;204(3):236-9

17. “[Behavior of papillary capillaries in initial common psoriasis.]” Schlosser and Pullmann, Zeitschrift fur Hautkrankheiten 1978 Oct 15;53(20):737-9

18.Overexpression of the angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase in psoriatic epidermis.” Creamer et al, The British Journal of Dermatology 1997 Dec;137(6):851-5

19.Effect of nerve growth factor on endothelial cell biology: proliferation and adherence molecule expression on human dermal microvascular endothelial cells.” Raychaudhuri et al, Archives for Dermatological Research 2001 Jun;293(6):291-5

20.Scatter factor (hepatocyte growth factor) is a potent angiogenesis factor in vivo.” Rosen et al, Symposia of the Society for Experimental Biology 1993;47:227-34

21.Induction of human microvascular endothelial tubular morphogenesis by human keratinocytes: involvement of transforming growth factor-alpha.” Ono et al, Biochemical and Biophysical Research Communications 1992 Dec 15;189(2):601-9

22.Overexpression of transforming growth factor alpha in psoriatic epidermis.” Elder et al, Science 1989 Feb 10;243(4892):811-4

23.Serum samples from patients with active psoriasis enhance lymphocyte- induced angiogenesis and modulate endothelial cell proliferation.” Majewski et al, Archives of Dermatology 1987 Feb;123(2):221-5

24.Metalloelastase (MMP-12) and 92-kDa gelatinase (MMP-9) as well as their inhibitors, TIMP-1 and -3, are expressed in psoriatic lesions.” Suomela et al, Experimental Dermatology 2001 Jun;10(3):175-83

25.Levels of endothelial cell stimulating angiogenesis factor and vascular endothelial growth factor are elevated in psoriasis.” Bhushan et al, The British Journal of Dermatology 1999 Dec;141(6):1054-60

26.Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells.” Detmar et al, The Journal of Investigative Dermatology 1995 Jul;105(1):44-50

27.Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis.” Detmar et al, The Journal of Experimental Medicine 1994 Sep 1;180(3):1141-6

28.The role of VEGF and thrombospondins in skin angiogenesis.” Detmar, Journal of Dermatological Science 2000 Dec;24 Suppl 1:S78-84

29.Genotype association of C(-735)T polymorphism in matrix metalloproteinase 2 gene with G(8002)A endothelin 1 gene with plaque psoriasis.” Vasku et al, Dermatology 2002;204(4):262-5

30.Immunohistochemical evaluation of psoriatic plaques following selective photothermolysis of the superficial capillaries.” Hern et al, The British Journal of Dermatology 2001 Jul;145(1):45-53

31.Elevated plasma levels of vascular endothelial growth factor and plasminogen activator inhibitor-1 decrease during improvement of psoriasis.” Nielsen et al, Inflammation Research 2002 Nov;51(11):563-7

32.Psoriasis: the future.” Kirby and Griffiths, The British Journal of Dermatology 2001 Apr;144 Suppl 58:37-43

33.Radicicol, a microbial cell differentiation modulator, inhibits in vivo angiogenesis.” Oikawa et al, European Journal of Pharmacology 1993 Sep 14;241(2-3):221-7

34.Endothelial cell stimulating angiogenesis factor.” Weiss and McLaughlin, The International Journal of Biochemistry & Cell Biology 1998 Apr;30(4):423-7

35.Antisense oligonucleotides inhibit vascular endothelial growth factor/vascular permeability factor expression in normal human epidermal keratinocytes.” Smyth et al, The Journal of Investigative Dermatology 1997 Apr;108(4):523-6

36.VEGF antagonists.” Hasan and Jayson, Expert Opinion on Biological Therapy 2001 Jul;1(4):703-18

37.Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2.” Hernandez et al, The Journal of Experimental Medicine 2001 Mar 5;193(5):607-20

38.Cyclosporine is angiostatic.” Norrby, Experientia 1992 Dec 1;48(11-12):1135-8

39.Cyclosporine inhibits basic fibroblast growth factor-driven proliferation of human endothelial cells and keratinocytes.” Sharpe et al, Archives of Dermatology 1989 Oct;125(10):1359-62

40.Effects of systemic etretinate treatment on natural cytotoxicity, immune angiogenesis and neutrophil adherence in patients with various forms of psoriasis.” Majewski et al, Archivum Immunologiae et Therapiae Experimentalis 1989;37(3-4):459-64

41.Three novel synthetic retinoids, Re 80, Am 580 and Am 80, all exhibit anti-angiogenic activity in vivo.” Oikawa et al, European Journal of Pharmacology 1993 Nov 2;249(1):113-6

42.Retinoids downregulate vascular endothelial growth factor/vascular permeability factor production by normal human keratinocytes.” Weninger et al, The Journal of Investigative Dermatology 1998 Nov;111(5):907-11

43.Regulation of vascular endothelial growth factor expression in human keratinocytes by retinoids.” Diaz et al, The Journal of Biological Chemistry 2000 Jan 7;275(1):642-50

44.Antiangiogenic properties of a novel shark cartilage extract: potential role in the treatment of psoriasis.” Dupont et al, Journal of Cutaneous Medicine and Surgery 1998 Jan;2(3):146-52 (also here)

45.Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis.” Sauder et al, Journal of the American Academy of Dermatology 2002 Oct;47(4):535-41