Vascular involvement in systemic sclerosis (scleroderma)

Pattanaik, Debendra; Brown, Monica; Postlethwaite, Arnold E.

doi:10.2147/jir.s18145

Cited by 44 publications

(43 citation statements)

References 225 publications

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“…Endothelial damage contributes to ongoing platelet aggregation with release of a member of fibrogenic mediators such as TGFβ1, TGFβ2, IL-4, platelet derived growth factor (PDGF), connective tissue factor, sphingosine 1-phosphate and lysophosphatidic acid [252]. Defective angiogenesis, neointimal proliferation and vascular spasm contribute to tissue hypoxia further stimulating ECM deposition [252]. There is also predominance of Th17 and Th2 cells with release of IL-17, IL-4 and IL-13 at sites of lymphocytic infiltration which contributes to ongoing fibrosis [252].…”

Section: Role Of Local Steroidogenic Pathways In Inflammatory Disomentioning

confidence: 99%

Steroidogenesis in the skin: Implications for local immune functions

Slominski

Zbytek

Nikolakis

et al. 2013

The Journal of Steroid Biochemistry and Molecular Biology

318

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The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7 -steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases.

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Section: Role Of Local Steroidogenic Pathways In Inflammatory Disomentioning

confidence: 99%

Steroidogenesis in the skin: Implications for local immune functions

Slominski

Zbytek

Nikolakis

et al. 2013

The Journal of Steroid Biochemistry and Molecular Biology

318

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“…Damage in the endothelium seems to be the initial lesion responsible for the cascade of events that results in the disease [4, 5] leading three main types of alterations: vascular occlusion, immune system alterations, and connective tissue proliferation.…”

Section: Introductionmentioning

confidence: 99%

Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

López-Cacho

Gallardo

Paz

et al. 2014

BioMed Research International

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This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies.

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“…There are excellent descriptions about the morphology of vasculitis and vascular changes in SSc [24][25][26][27], but these do not mention the prevalence in percent, neither in various organs, nor in mortality. Most of the autopsy studies focus on organ involvement only [26,27,28].…”

Section: Prevalence and Nature Of Sv In Sscmentioning

confidence: 99%