Quantitative comparison of angiogenesis and lymphangiogenesis in cutaneous lichen planus and psoriasis: Immunohistochemical assessment
Introduction
The cutaneous microcirculation in healthy adults is predominantly quiescent, due to the dominant influence of endogenous angiogenesis inhibitors over the stimuli. However it retains the capacity for brisk initiation of angiogenesis and lymphangiogenesis in specific physiological and pathological conditions.
Experimental studies have revealed that angiogenesis and lymphangiogenesis are tightly connected, not only in tumor biology, but also in chronic inflammation. Pathological angiogenesis or lymphangiogenesis was confirmed in skin tumors: melanoma (Hannah and Folkman, 1996, Marcoval et al., 1996, Kashani-Sabet et al., 2002, Jonjic et al., 2003), basal cell carcinoma (Staibano et al., 1996), Kaposi's sarcoma (Kang et al., 2008), hemangioma (Boye et al., 2001) as well as in chronic dermatoses such as rosacea (Aroni et al., 2008), atopic dermatitis (Zhang et al., 2006, Genovese et al., 2012) and especially in psoriasis (Braverman and Sibley, 1982, Creamer et al., 1997, Creamer et al., 2002a, Heidenreich et al., 2009).
Both psoriasis and cutaneous lichen ruber planus (CLP) are relatively common chronic inflammatory dermatoses with unclear etiology and not entirely understood pathogenesis. Both of these dermatoses are classified in the group of primarily T-lymphocyte – driven diseases (Braun-Falco et al., 2001). Both psoriasis and cutaneous lichen planus show key histopathological changes in lesional epidermis and concomitant inflammatory changes within the dermis.
Histopathological manifestation of CLP includes epidermal hyperkeratosis with zonal wedge-shaped hypergranulosis and little or no parakeratosis, the basal cells vacuolar alteration, acanthosis and colloid bodies as anucleated remnants of apoptotic basal keratinocytes. A band like lymphocytic infiltrate occupies the widened papillary dermis and may be admixed with melanophages (Murphy, 1995, Lehman et al., 2009, Joshi, 2013).
Major characteristics of lesional psoriatic skin include epidermal hyperplasia with elongated rete ridges, abnormal differentiation of the keratinocytes, spongiosis, parakeratosis and hypogranulosis. Within the dermis there is an accumulation of inflammatory cells, especially T-lymphocytes, monocytes and neutrophils, and prominent expansion of the superficial vascular plexus with high and tortuous capillary loops within the dermal papillae (Braverman and Sibley, 1982, Braun-Falco et al., 2001, Murphy et al., 2007).
Currently there is increasing evidence that psoriasis is an angiogenesis – dependent disease, however microvascular changes in cutaneous lichen planus are rarely reviewed. Angioproliferation was confirmed only in mucous-oral lichen planus (Scardina et al., 2007a, Scardina et al., 2007b, Scardina et al., 2011, Tao et al., 2007, Scardina and Mesina, 2009). Therefore the objective of the present study was the immunohistochemical assessment of quantitative changes of both the blood and lymphatic microcirculatory beds within CLP lesions and its comparison with psoriatic lesions and healthy skin.
Section snippets
Tissue samples
Twenty-one skin samples of CLP lesions and 22 skin samples of psoriatic lesions were taken from untreated patients without any systemic disorder. Another 20 control healthy skin samples from subjects without skin and systemic disease were excised from the same topographical regions as the pathological samples and were included in this study. On the basis of our preliminary study, all samples were taken from individuals aged 31–57 years of both genders to eliminate age-dependent variability of
Results
Criteria for histopathological diagnosis of CLP and psoriasis were confirmed in all CLP and psoriatic samples (Fig. 1). Blood vessels area (BVA) and lymphatic vessels area (LVA) were evaluated within the papillary dermis of the skin using the double immunohistochemical staining (Fig. 2, Fig. 3). VEGF and VEGF-C positive areas were determined within the dermis and epidermis separately. All these parameters were quantified in cutaneous lichen planus lesions, psoriatic lesions and control healthy
Discussion
Blood microcirculation in the skin is arranged in two plexuses: a deep reticular plexus and a superficial subpapillary plexus (Braverman, 1989, Braverman, 2000). The lymphatic vasculature also forms two plexuses in vicinity to the blood vessels (Ryan et al., 1986, Skobe and Detmar, 2000).
Under certain circumstances the skin microcirculation can be stimulated to angiogenesis and lymphangiogenesis which are strictly controlled processes of new blood and lymphatic vessels development from
Conclusion
Finally, we can suppose that angiogenesis and lymphangiogenesis are tightly connected not only to pathogenesis of psoriasis but also to cutaneous lichen planus. Our results indicate more considerable level of angiogenesis in psoriatic lesions than in CLP lesions but the same level of lymphangiogenesis in both skin lesions. Vascular activation maintains the inflammatory processes.
Regulation of angiogenesis in tumor biology has been well studied and clinically implemented in anti-angiogenic
References (61)
The cutaneous microcirculation
J Invest Dermatol Symp Proc
(2000)- et al.
Role of microcirculation in the treatment and pathogenesis of psoriasis
J Invest Dermatol
(1982) - et al.
Ultrastructure of the capillary loops in the dermal papillae of psoriasis
J Invest Dermatol
(1977) - et al.
Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells
J Invest Dermatol
(1995) The role of VEGF and thrombospondins in skin angiogenesis
J Dermatol Sci
(2000)Evaluation of angiogenesis in normal and lichen planus skin by CD34 protein immunohistochemistry: preliminary findings
Cell Biol Int
(2007)- et al.
Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution
Blood
(2009) - et al.
The histopathologic spectrum of psoriasis
Clin Dermatol
(2007) - et al.
Structure function, and molecular control of the skin lymphatic system
J Invest Dermatol Symp Proc
(2000) - et al.
The prognostic significance of tumor angiogenesis in nonaggressive and aggressive basal cell carcinoma of the human skin
Hum Pathol
(1996)
Lymphangiogenesis: molecular mechanisms and future promise
Cell
Assessment of local angiogenesis and vascular endothelial growth factor in the patients with atrophic-erosive and reticular oral lichen planus
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
Angiogenesis in wound healing
J Invest Dermatol Symp Proc
The angiogenesis inhibitor thrombospondin-1 inhibits acute cutaneous hypersensitivity reactions
J Invest Dermatol
Angiogenesis
A study of the pathogenesis of rosacea: how angiogenesis and mast cells may participate in a complex multifactorial process
Arch Dermatol Res
Quantification of microvascular changes in the skin in patients with psoriasis
Br J Dermatol
Clonality and altered behavior of endothelial cells from hemangiomas
J Clin Invest
Dermatológia a venerológia
Ultrastructure and organisation of the cutaneous microvasculature in normal and pathological stages
J Invest Dermatol
Clinical, pathological and immunological features of psoriatic-like lesions affecting keratin 14-vascular endothelial growth factor transgenic mice
Histol Histopathol
Mechanisms of angiogenesis and arteriogenesis
Nat Med
Angiogenesis in health and disease
Nat Med
Localisation of endothelial proliferation and microvascular expansion in active plaque psoriasis
Br J Dermatol
Mediation of systemic vascular hyperpermeability in severe psoriasis by circulating vascular endothelial growth factor
Arch Dermatol
Angiogenesis in psoriasis
Angiogenesis
Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis
J Exp Med
Digging deeper into lymphatic vessel formation in vitro and in vivo
BMC Cell Biol
Vascular endothelial growth factor: basic science and clinical progress
Endocr Rev
Angiogenesis, lymphangiogenesis and atopic dermatitis
Chem Immunol Allergy
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