Advances In Research On Microcirculation Changes Of Psoriasis Skin

Psoriasis is a common chronic, relapsing, inflammatory skin disease with obvious seasonality. It recurs or aggravates in winter and relieves in summer, which seriously affects the aesthetics and quality of life of patients. The exact pathogenesis is still unclear and is currently considered to be related to genetic factors, environmental factors, and immune factors. In recent years, the role of skin microcirculation changes in the pathogenesis of psoriasis has received increasing attention. The microcirculation of the skin is divided into microvessels and microlymphatic vessels, which are mainly distributed in the dermis layer and the subcutaneous fat layer. The microvessels are composed of terminal small arteries, arteriovenous capillaries, and posterior venules. Psoriasis patients with lesions, non-lesional lesions, skin microcirculation and hyperthyroidism microcirculation have varying degrees of damage, including microvascular, microlymphatic vessels, blood flow, hemorheology, and changes in endothelial function.

Psoriasis microvascular changes

1. 1 Microvascular morphology changes

Morphological changes in skin microvessels are the earliest histological changes detectable in psoriasis. Microvascular abnormalities are characteristic in the pathological changes of psoriasis and play a fundamental role in the development of diseases. The vascular network of psoriatic lesions is very developed, especially in the dermal nipple of edema, the number of capillaries increases, is distorted, the diameter of the tube is widened and expanded, the appearance is hemangioma-like, and the capillary-like hairpin-like structure is prolonged. Twisted into a group, similar to the structure of the glomerulus, there is obvious oozing around. The capillary iliac arteries are characterized by veins, such as the uniform structure of the vascular basement membrane transforming into a non-uniform monolayer or multi-layer structure and a bridging window between the endothelium, resulting in increased permeability of the wall, and these changes are also seen in the lesions. The surrounding appearance is normal in the skin. Compared with the non-lesional lesions, the surface area of ​​the vascular endothelium was increased by nearly 4 times, and the distance between endothelial cells was widened. Vascular changes already exist before epidermal hyperplasia occurs. As a systemic disease, hyperthyroidism in patients with psoriasis without a nail is also abnormal, especially in patients with psoriasis. Ribeiro et al found that the patients with psoriasis had narrow capillary stenosis and reduced density. Chinese scholars have found that patients with hyperthyroidism microcirculation disorders mainly manifested as tube stenosis blur shortening, bending deformity, periorbital exudation, dome stenosis more common, the input branch vessels become thinner, the output branch vessels thickened, periorbital hemorrhage, obstacles The degree is positively correlated with the severity of the condition.

1. 2 Neovascularization

It is currently believed that neovascularization is one of the pathogenesis of psoriasis. Neovascularization provides nutrients to proliferating keratinocytes and tissues, promotes inflammatory cell migration, and is critical for the development and persistence of psoriasis. Studies have shown that tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), endothelial cell stimulating vascular growth factor (ESAF), platelet-derived endothelial growth factor/deoxythymidine phosphorylase (PDECGE/TP) Increased levels of pro-angiogenic mediators such as transforming growth factor (TGF), platelet-derived factor (PDGF), hypoxia-inducible factor (HIF), and interleukin-8 (IL8); in promoting angiogenesis, helper T cells 17 (Th17) Secreted interleukin-17 (IL17) also played a role. Angiopoietin VEGF-A and VEGF-B stimulate angiogenesis by binding to the vascular endothelial cell surface receptor VEGFR1, which determines the proliferation and migration of vascular endothelial cells and increased vascular permeability. In genetically modified mice, overexpression of VEGF induces psoriasis-like lesions, and systemic anti-VEGF and receptor therapy in a psoriasis mouse model inhibits skin inflammation, inflammatory cell infiltration, and angiogenesis. In vascular endothelial cells at the lesion, IL-36γ is highly up-regulated in mRNA translation and protein expression levels, and is associated with elevated levels of IL-17, IL23, and TNF-α, which can be directly or indirectly involved in angiogenesis. IL-36γ-mediated local endothelial cell secretion of IL-8 promotes vascular proliferation in the lesion site. The chemokine-like growth factor (CKLF1) and its receptor CCR4 were highly expressed in the lesion site, and the expression was up-regulated under the stimulation of TNF-α in the local microenvironment. CKLF1-derived peptides C19 and C27 promote hyperplasia of the dermal microcirculation while causing hyperplasia of the epidermis. In the lesions, keratinocytes over-express IL-33, which mediates the secretion of VEGF by mast cells and promotes vascular proliferation. Mesenchymal stem cells are particularly important in angiogenesis due to their potential for transdifferentiation and angiogenesis. The local microenvironment of lesions induces the production of vascular and inflammatory mediators by mesenchymal stem cells. Promotes early angiogenic events and reduces vascular endothelial cell permeability through a mechanism of paracrine and direct cell contact. The expression of EDIL3, AMOT and ECM1 genes was highly expressed in mesenchymal stem cells at the lesion. EDIL3 is a microcellular extracellular matrix protein that promotes angiogenesis and endothelial skeletal formation and may prevent endothelial cell apoptosis by inducing expression of the Bcl-2 gene. ECM1 acts as a novel paracrine factor that stimulates vascular endothelial cell proliferation and angiogenesis. AMOT is a receptor for the angiogenesis inhibitor angiostatin, which plays a role in specific endothelial cell-targeted traction and angiogenesis.

2.Changes in psoriasis microlymphatic vessels

Compared with microvascular changes, the changes of microlymphatic vessels in psoriasis are easily overlooked. The dermal papillary lymphatic vessels and capillary lymphatic vessels in the lesions are hyperplasia, density is increased, and the diameter of the vessels is significantly expanded. Histological studies have found that lymphatic vessels are deeper from the dermis. 5倍倍。 The upward movement, the drainage rate increased, the permeability increased by 7.5 times than normal. Neoplastic lymphangiogenesis is observed in lesions in a psoriasis mouse model, and lymphopoietin VEGF-C and VEGF-D secreted by mast cells and macrophages regulate lymphoids by activating lymphatic endothelial cell surface receptor VEGFR-3R Tube generation. Angiopoietin promotes vascular regeneration in the skin and also promotes lymphangiogenesis. Excessive expression of VEGF-A in the epidermis alters the physiological function of the lymphatic vessels of the skin, promotes pathological lymphangiogenesis and expansion, and inhibits VEGF-A and its receptors to reduce the density of lymphatic microcirculation. Type I transmembrane glycoprotein (LYVE-1) is a lymphatic specific marker for the skin. Lymphocyte endothelial cell VEGFA mediates LYVE-1 lytic cleavage via the ERK pathway and disintegrin metalloproteinase 17 (ADAM17), causing its extracellular domain to shed. In the psoriatic lesions, immunohistochemistry can be used to observe the detachment of LYVE-1 extracellular domain, suggesting that this change may play a role in the formation of lymphangiogenesis.

3. Psoriasis skin microcirculation blood flow changes

3. 1 Changes in blood flow

The Doppler laser blood flow meter was used to observe the local microcirculation blood perfusion of psoriatic lesions. In the plaques with the same appearance, the blood perfusion intensity showed obvious heterogeneity, non-skin lesions. The blood perfusion intensity of the site also increased significantly. The blood flow of the lesions increased by 9 to 13 times compared with healthy people, and the surrounding normal skin increased by 2. 5 to 4. 5 times. The blood perfusion of the lesions was 144% of the non-lesional lesions, and gradually decreased after effective treatment. There was an increase in blood flow within 4 mm of the plaque diameter, but no changes in epidermal changes and inflammatory cell infiltration were observed, further indicating that microcirculatory blood flow increased before histological changes, which may be an indicator of skin inflammation, angiogenesis and plaque progression. . However, the blood perfusion of the hyperthyroid microcirculation in patients with psoriasis is lower than that of normal people. On the one hand, it may be because the function of vascular endothelial cells is more complicated. On the other hand, it may be because psoriasis has the same function as atherosclerosis. The basis of the disease, the specific reasons need further study and clarification.

3. 2 Hemorheological changes

Vaya et al. found that fibrinogen levels, plasma viscosity, and red blood cell aggregation in patients with psoriasis were higher than in healthy people. These changes in hemorheological parameters may be caused by metabolic abnormalities and inflammatory reactions. The deformability of red blood cells refers to the ability of red blood cells to change their shape when passing through microcirculation to facilitate passage. Gornicki et al found that the viscosity of red blood cells in patients with psoriasis increased, the average volume of red blood cells decreased, and the deformability of red blood cells decreased, and the activity of Na+-K+-ATPase and the decrease of Ca2+-Mg2+ATPase activity also played a role. Under high shear force and low shear force, the patient’s red blood cell deformability did not decrease, and the mean hemoglobin concentration (CHCM), the mean red blood cell volume (MCV), and the red blood cell mean hemoglobin (HCM) were not different from those of healthy people. The blood flow resistance index of the hyperthyroid microcirculation in patients with psoriasis increased, and the blood flow resistance of the nailfold microcirculation of the psoriasis was increased more than that of the psoriasis without a nail. Vascular resistance depends on three factors: vessel diameter (r), vessel length (L), blood viscosity (n), and resistance R = (L·n) / r4. Psoriasis hyperthyroidism microcirculatory vascular resistance and blood flow reduction may be due to vascular endothelial cell dysfunction and inflammatory state of the wall thickening, vascular diameter is reduced.

3. 3Changes in vascular endothelial function

The results of studies on vascular function changes in patients with psoriasis are not completely consistent. Numerous studies have shown that vascular function is impaired in patients with moderate to severe psoriasis, and endothelial function damage, oxidative stress, and vascular inflammation are the basis for the risk of high cardiovascular disease in patients with psoriasis. Sharma and other psoriatic arthritis patients with impaired vascular endothelial function, even if the injury has not yet occurred, the risk of endothelial damage is higher than normal, sublingual nitroglycerin can improve endothelial function, indicating the release of endothelial cells Nitrogen reduction is the cause of impaired endothelial function. However, Hayek et al. found no statistically significant differences in vascular endothelial function and arterial stiffness between patients with moderate psoriasis and healthy controls. After treatment with etanercept, clinical symptoms were relieved but vascular function was not affected before and after treatment.

4. Skin microcirculation and psoriasis treatment

Microcirculation changes have occurred in patients with clinical signs and lesions of psoriasis. After effective treatment and clinical remission, microcirculatory abnormalities begin to recover. Compared with the natural course of disease, the total perfusion of the lesions treated with topical betamethasone dipropionate/caliperol cream was reduced, erythema, infiltration and desquamation were reduced, and the SUM score was reduced. Etanercept is a TNF receptor fusion protein that blocks its angiogenic function and causes a decrease in the number of dermal blood vessels. After systemic administration of etanercept, the abnormal microcirculation morphology of the lesions gradually recovered, and the clinical PASI score decreased. The change was more obvious with the treatment time, but in patients with complete clinical symptoms, microcirculation abnormalities still exist. May be the structural basis for the recurrence of psoriasis. The same results were also seen after topical application of mometasone furoate cream and cyclosporine after systemic administration. After treatment with biological agents, the clinical symptoms and microcirculation abnormalities were restored, the inflammation index decreased, and the hemorheology abnormalities also became normal.

5 Conclusion

Microcirculation changes are important histopathological changes in psoriasis. Structural and functional changes occur under the influence of various pathogenic factors, causing the occurrence and maintenance of inflammatory reactions. The microcirculation changes before the onset of clinical symptoms, and the clinical symptoms begin to gradually relieve after the microcirculation abnormalities begin to recover after treatment. Therefore, microcirculatory changes can be used as an effective indicator for assessing disease severity, drug efficacy, and disease monitoring. Early studies on the microcirculation of psoriasis in China mainly focused on the changes of the microcirculation of the hyperthyroidism, and there were few reports on the microcirculation changes in the lesions. With the maturity of laser Doppler blood flow imaging technology and the promotion of laser Doppler blood flow meter, it is possible to monitor the skin microcirculation blood flow changes by using non-invasive techniques in real time.