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COMMENTARY
Year : 2020  |  Volume : 13  |  Issue : 1  |  Page : 95-96  

Study of dermal vascular changes in inflammatory skin diseases


Department of Pathology, Sri Devaraj Urs Medical College, Kolar, Karnataka, India

Date of Web Publication16-Dec-2019

Correspondence Address:
Subhashish Das
Department of Pathology, Sri Devaraj Urs Medical College, Kolar, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_83_18

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How to cite this article:
Das S. Study of dermal vascular changes in inflammatory skin diseases. Med J DY Patil Vidyapeeth 2020;13:95-6

How to cite this URL:
Das S. Study of dermal vascular changes in inflammatory skin diseases. Med J DY Patil Vidyapeeth [serial online] 2020 [cited 2020 Jul 7];13:95-6. Available from: http://www.mjdrdypv.org/text.asp?2020/13/1/95/272890



The changes of cutaneous vascular system in chronic skin inflammation are very important because in inflamed skin, vascular remodeling consists of a hyperpermeable, enlarged network of vessels with increased blood flow, and influx of inflammatory cells. During chronic inflammation, the activated endothelium expresses adhesion molecules, cytokines, and other molecules that lead to leukocyte rolling, attachment, and migration into the skin. Recent studies reveal that inhibition of blood vessel activation exerts potent anti-inflammatory properties.[1]

Angiogenesis and lymphangiogenesis, the growth of new vessels from preexisting ones, have received increasing interest due to their role in tumor growth and metastatic spread. However, vascular remodeling, associated with vascular hyperpermeability, is also a key feature of many chronic inflammatory diseases including asthma, atopic dermatitis, psoriasis, and rheumatoid arthritis. The major drivers of angiogenesis and lymphangiogenesis are vascular endothelial growth factor (VEGF)-A and VEGF-C, activating specific VEGF receptors on the lymphatic and blood vascular endothelium.[2]

The main vascular changes during inflammation consist of vascular enlargement, whereas tumor growth is mainly associated with sprouting angiogenesis. However, vascular hyperpermeability and endothelial cell proliferation are common to both types of angiogenesis.[3] The effect of blocking VEGF-A and angiogenesis is extensively investigated in human cancers but warrants further investigation in inflammatory processes.[4]

Blood vessels and, to a lesser extent, lymphatic vessels contribute essentially to the cardinal signs of inflammation: Dilated blood vessels with increased flow underlie the “rubor” and the “calor;” the excess exudate caused by hyperpermeable blood vessels exceeding the drainage capacity of fluid by lymphatic vessels results in “tumor.” Finally, “dolor” and “functio laesa” are subsequent processes following vascular activation and influx of leukocytes.[5]

Activation of the endothelium by inflammatory mediators (such as VEGF-A, tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) leads to the upregulation of adhesion molecules such as E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell-adhesion molecule-1, which enables the interaction with leukocytes.[6] In chronic inflammatory diseases, the vasculature remains activated, enlarged, and hyperpermeable, and it sustains the accumulation of fluid (edema) and cells. Considerable amounts of plasma proteins extravasate from the blood into the tissue during inflammation.[7]

The inflammatory skin diseases associated with prominent remodeling of the vasculature range from ultraviolet damage, bullous pemphigoid, contact dermatitis, to rosacea and psoriasis. Vascular remodeling is controlled by pro- and anti-angiogenic mediators. An imbalance leads to vessel growth or regression.[8]

The vascular response in inflammatory skin lesions is characterized by the following salient features:[9]

  • Patterns are the result of the interaction of injury agents and tissue response, modulated in intensity and time
  • Elementary lesions will depend on:


    • Basic epidermal reaction (based on cellular turnover and maturation)
    • Vascular and cellular inflammatory components
    • Types of cells


  • Distribution of cells (topography and microanatomy).
  • Activity should be evaluated from target damage (epithelial, necrosis, vasculitis), exocytosis (neutrophilic), and density of infiltrate.



  Conclusion Top


There is now extensive evidence that targeting the activated, remodeled blood vessels might represent a novel and promising therapeutic approach for treating chronic inflammatory diseases – not only of the skin. The status of vascular activation might also be used as a biomarker for the intensity and activity of inflammatory diseases. Importantly, our recent findings indicate that activation of lymphatic vessels might serve as a novel strategy for treating chronic inflammatory disorders such as psoriasis, rosacea, chronic airway inflammation, rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis.[1]

There is clear evidence that in humans, vascular remodeling occurs in many chronic inflammatory disorders. Even though different anti-inflammatory drugs are on the market, there is no specific therapy that interferes with the pathological vascular changes that occur during inflammation. Angiogenesis and lymphangiogenesis are tightly linked to chronic inflammation, and targeting the blood vessels and lymphatic vessels has been shown to be an effective strategy in different experimental mouse models of chronic inflammation.[2]



 
  References Top

1.
Huggenberger R, Detmar M. The cutaneous vascular system in chronic skin inflammation. J Investig Dermatol Symp Proc 2011;15:24-32.  Back to cited text no. 1
    
2.
Zgraggen S, Ochsenbein AM, Detmar M. An important role of blood and lymphatic vessels in inflammation and allergy. J Allergy (Cairo) 2013;2013:672381.  Back to cited text no. 2
    
3.
Feng D, Nagy JA, Pyne K, Hammel I, Dvorak HF, Dvorak AM. Pathways of macromolecular extravasation across microvascular endothelium in response to VPF/VEGF and other vasoactive mediators. Microcirculation 1999;6:23-44.  Back to cited text no. 3
    
4.
Brown LF, Harrist TJ, Yeo KT, Ståhle-Bäckdahl M, Jackman RW, Berse B, et al. Increased expression of vascular permeability factor (vascular endothelial growth factor) in bullous pemphigoid, dermatitis herpetiformis, and erythema multiforme. J Invest Dermatol 1995;104:744-9.  Back to cited text no. 4
    
5.
Yano K, Oura H, Detmar M. Targeted overexpression of the angiogenesis inhibitor thrombospondin-1 in the epidermis of transgenic mice prevents ultraviolet-B-induced angiogenesis and cutaneous photo-damage. J Invest Dermatol 2002;118:800-5.  Back to cited text no. 5
    
6.
Kunstfeld R, Hirakawa S, Hong YK, Schacht V, Lange-Asschenfeldt B, Velasco P, et al. Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia. Blood 2004;104:1048-57.  Back to cited text no. 6
    
7.
Gomaa AH, Yaar M, Eyada MM, Bhawan J. Lymphangiogenesis and angiogenesis in non-phymatous rosacea. J Cutan Pathol 2007;34:748-53.  Back to cited text no. 7
    
8.
Karpanen T, Alitalo K. Molecular biology and pathology of lymphangiogenesis. Annu Rev Pathol 2008;3:367-97.  Back to cited text no. 8
    
9.
Nagy JA, Vasile E, Feng D, Sundberg C, Brown LF, Detmar MJ, et al. Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med 2002;196:1497-506.  Back to cited text no. 9
    




 

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