Capillaroscopic pattern in systemic sclerosis — an association with dynamics of processes of angio- and vasculogenesis
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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2020, Revista Colombiana de ReumatologiaMicrovascular abnormalities in asymptomatic chronic smokers: A videocapillaroscopic study
2019, Microvascular ResearchCitation Excerpt :Additionally, various connective tissue diseases—such as systemic sclerosis, systemic lupus erythematosus, dermatomyositis, polymyositis, rheumatoid arthritis, primary Sjögren's syndrome, and familial Mediterranean fever—have been examined via nailfold videocapillaroscopy Cutolo et al., 2013; Dinc et al., 2001; Nagy and Czirjak, 2004; Yuksel et al., 2014). The most common of these is systemic sclerosis, in which vascular injury is accepted as the primary incident in its pathogenesis (Lambova and Müller-Ladner, 2010). Moreover, primary and secondary Raynaud's phenomenon have been easily distinguished via nailfold videocapillaroscopy (Beltrán et al., 2007).
Capillaroscopic findings and vascular biomarkers in systemic sclerosis: Association of low CD40L levels with late scleroderma pattern
2016, Microvascular ResearchCitation Excerpt :Impaired angiogenic response, one of the defective mechanisms of vascular repair during SSc, was shown to be related to the imbalance between pro-angiogenic and angiostatic factors (Manetti et al., 2010). Of the pro-angiogenic factors; vascular endothelial growth factor (VEGF), transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), interleukin-8 (IL-8), adhesion molecules such as P-selectin and E-selectin and their soluble forms were found to be increased in SSc patients, TGF-β1 and MCP-1 were found to be related to proliferative vasculopathy and fibrosis (Varga and Abraham, 2007; Wigley, 2009; Distler et al., 2009; Kuryliszyn-Moskal et al., 2005; Lambova and Müller-Ladner, 2010; Abraham and Distler, 2007; Hummers et al., 2009; Barnes et al., 2011). Tissue plasminogen activator (t-PA) is one of the members of the fibrinolytic system, reported to be increased in SSc patients and decreased after treatment with prostaglandin analogs (Bandinelli et al., 2005).
Prevalence and evolution of scleroderma pattern at nailfold videocapillaroscopy in systemic sclerosis patients: Clinical and prognostic implications
2015, Microvascular ResearchCitation Excerpt :Vascular involvement plays a decisive role in SSc pathogenesis occurring early in the course of disease, typically with the appearance of Raynaud's phenomenon (Kahaleh, 2004). Microangiopathy is also directly responsible for some severe clinical manifestations, such as digital ulceration, pulmonary arterial hypertension and scleroderma renal crisis (Lambova and Müller-Ladner, 2010). Capillaroscopy is an imaging technique, for the in vivo study of microcirculation, quick to perform, non-invasive, and not expansive (Grassi and De Angelis, 2007; Ingegnoli et al., 2013a).
Vascular biomarkers and correlation with peripheral vasculopathy in systemic sclerosis
2015, Autoimmunity ReviewsCitation Excerpt :In this review, we focus the attention on the involvement of the microvasculature and present the main vascular biomarkers and their reported associations with the vascular features of the disease. The damage of the microvessels evolves progressively from the early to the late stages in SSc, with different morphological abnormalities that are clearly shown by nailfold videocapillaroscopy (NVC) changes during the disease evolution [14–18]. These modifications are often accompanied by abnormal levels of angiogenic/angiostatic factors and markers of EC activation and injury.