Elsevier

Microvascular Research

Volume 80, Issue 3, December 2010, Pages 534-539
Microvascular Research

Capillaroscopic pattern in systemic sclerosis — an association with dynamics of processes of angio- and vasculogenesis

https://doi.org/10.1016/j.mvr.2010.07.005Get rights and content

Abstract

Мicrocirculation is the main environment of the pathologic processes in systemic sclerosis (SSc). Nailfold capillaroscopic abnormalities in SSc are highly specific. It is well known that capillaroscopic examination reveals different changes in the different stages of SSc. Dilated, single giant capillaries and haemorrhages, preserved arrangement are the characteristic features of the “early” capillaroscopic phase; frequent giant capillaries and haemorrhages are the findings in the “active” phase, while in the “late” stages extensive avascular areas are usually found. Although tissue hypoxia normally is a strong inducer of neovascularization, there is no evidence of significant vascular recovery in SSc patients. Formation of new blood vessels is possible through two different mechanisms – angiogenesis (formation of new vessels from differentiated endothelial cells of prior vessels) – and vasculogenesis (from endothelial progenitor cells—EPCs). Disturbed function of EPCs has been found in all the stages of the disease. Only EPCs from SSc patients in the early phase of the disease have shown preserved ability for differentiation and maturation to endothelial cells in vitro. The recovery of the injured microvessels is also disturbed due to a predominance of angiogenic inhibitors. The capillaroscopic changes in the different stages of SSc mirror the dynamics in processes of angio- and vasculogenesis. The formation of new capillaries after therapeutic influence of vascular recovery by transplantation of autologous bone-marrow derived stem cells supports this conclusion.

Introduction

Systemic sclerosis (SSc) is a chronic, multisystem connective tissue disorder, which affects the microcirculation, the skin and various internal organs. It is characterized by a triad of widespread microangiopathy, fibrosis, and autoimmune disturbances with activation of the humoral as well as cellular immune responses. There is an increasing evidence, which indicates that vascular damage is a primary event in the pathogenesis of SSc. The progressive vascular injury includes persistent endothelial damage, intimal thickening, vessel narrowing and obliteration. These changes lead to a reduced capillary blood flow with subsequent tissue ischemia and severe clinical manifestations such as digital ulceration, pulmonary arterial hypertension and scleroderma renal crisis. Although tissue hypoxia is a strong inducer of neovascularization, there is no evidence of significant vascular recovery in SSc patients. Different pathogenetic pathways lead to chronic tissue ischemia and result in irreversible structural changes of vascular architecture at different sites, capillary loss and inadequate, inefficient, reparative vascular recovery. The imbalance between pro-angiogenic and angiostatic factors may also contribute to the impaired angiogenic response in SSc. Although different proangiogenic stimuli exist in SSc, they do not elicit the appropriate angiogenic response (Manetti et al., 2010). Either angiogenic or vasculogenic mechanisms may potentially become in the future the target of therapeutic strategies to promote capillary regeneration in SSc (Miniati et al., 2009). Capillaroscopic pattern in SSc is specific and is observed in more than 90% of patients with overt SSc (Cutolo et al., 2000, Cutolo et al., 2005, Maricq et al., 1980). It allows specific capillaroscopic abnormalities to be used for the early diagnosis of SSc. The specific pattern in SSc is characterized by presence of dilated and giant capillaries, haemorrhages, avascular areas and neoangiogenesis. It was described for the first time by Maricq et al. (1980) and was termed — “scleroderma type” capillaroscopic pattern (Maricq et al., 1980). It is well-known that capillaroscopic findings in the early and late stages of the disease are distinctly diverse. Capillaroscopic changes in SSc are usually classified into three subtypes: – an “early” pattern – with appearance of few dilated and/or giant capillaries and few haemorrhages, relatively preserved distribution without loss of capillaries; an “active” pattern – with higher number of giant capillaries and haemorrhages, moderate loss of capillaries, slight derangement, diffuse pericapillary oedema and – a “late” pattern characterized by extensive avascular areas, severe derangement, ramified and bushy capillaries (Cutolo et al., 2000). The confluence of the avascular areas in the late stages of the disease leads to the characteristic desert-like appearance. Meandering capillaries, presence of more than one capillary loop in a single dermal papilla, ramified and bushy capillaries are the characteristic features of neoangiogenic capillaries, which are a proof of inadequate and abortive angiogenesis and can be found in the advanced stages of the disease.

In the present review, we have aimed to analyze the recent knowledge about the impaired vascular repair (e. g. angiogenesis and vasculogenesis) in the different stages of SSc.

Section snippets

Nailfold capillaroscopy in SSc

Nailfold capillaroscopy is a non-invasive, inexpensive and easy-to-repeat technique, which is of substantial value for the evaluation of microcirculation in vivo (Bollinger and Fagrell, 1990, Cortes and Cutolo, 2007, Shore, 2000). It is the only method for the evaluation of nutritional capillaries of the nailfolds. In the nailfold area, the capillary loops become more parallel to the skin surface, and in the last row they can be observed in their full length. The capillaries consist of an

Conclusion

Despite the severe tissue ischemia in SSc, which is a strong stimulus for the formation of new vessels, the vascular recovery in this disease is defective. The capillaroscopic changes in the different stages of SSc mirror the dynamics in processes of angio- and vasculogenesis. A more detailed analysis of the pathways underlying the defective angiogenesis and vasculogenesis in SSc may result in new future therapies.

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