Systemic sclerosis: vascular, pulmonary and immunological aspects

In systemic sclerosis (SSc), interstitial lung disease (ILD) and engagement of the vascular system result in improved morbidity and mortality. The purpose of this dissertation was to elucidate, in a consecutively included cohort of SSc (limited and diffuse) patients (n = 33), the T cell cytokine profile driving the disease in ILD and also to investigate the role of matrix metalloproteinase 9 (MMP-9) as well as its inhibitor: tissue inhibitor of metalloproteinase 1 (TIMP-1) in the extracellular matrix (ECM) degrading process resulting in fibrous scarring and honey combing. Furthermore, to characterize the role of nitric oxide (NO) in vascular engagement. Peripheral arterial changes trigger Raynaud’s phenomenon and digital ulcers. Nitric oxide (NO) a main inducer of vasodilation is created by endothelial nitric oxide synthase (eNOS) in reaction to adjustments in blood flow or by inflammatory cytokine inducible (i) NOS. In the vascular smooth muscle cell (VSMC) NO activates guanylate cyclase to produce cGMP, leading to relaxation. We demonstrated elevated plasma nitrate, a degradation product of NO, and increased urinary excretion of nitrate and cGMP…

Contents: Systemic sclerosis: vascular, pulmonary and immunological aspects

INTRODUCTION
SYSTEMIC SCLEROSIS
Definition
Disease criteria and classification of subsets
Overlap disorders
EPIDEMIOLOGY OF SYSTEMIC SCLEROSIS
Incidence and prevalence
Female to male ratio
Prevalence according to disease subsets
Age at peak incidence
5- and 10 years survival
Mortality in relation to disease subset
Causes of death
DISEASE MANIFESTATIONS IN SYSTEMIC SCLEROSIS
Skin changes
Clinical skin changes
Histopathology of the skin lesion
Endothelial cells
Leukocytes
Fibroblasts
Involvement of the gastro-intestinal tract
Oesophagus and stomach
Smaller and greater intestine
Cardiac involvement
Renal engagement
Pulmonary hypertension
ENDOTHELIAL FUNCTION IN SYSTEMIC SCLEROSIS
Introduction
Raynaud’s phenomenon
Endothelium-dependent dilation
Endothelium-independent dilation
ADHESION MOLECULES IN SYSTEMIC SCLEROSIS
Introduction
Soluble adhesion molecules and leukocyte expression of adhesion molecules
Adhesion molecules in the skin lesion
Adhesion molecules in interstitial lung disease
NITRIC OXIDE IN SYSTEMIC SCLEROSIS
Introduction
Circulating nitric oxide metabolites
Nitric oxide synthases in the skin lesion
Nitric oxide and lung disease
Nitric oxide and the proliferation of endothelial cells
Nitric oxide dependent mechanisms in the therapy of systemic sclerosis
INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS
Epidemiology
High resolution computed tomography
Broncho-alveolar lavage fluid cell count: relation to HRCT finding and lung function
Neutrophil alveolitis: relation to lung function, HRCT and prognosis
Immune mechanisms in neutrophil alveolitis
Neutrophil proteases
Myeloperoxidase
Neutrophil elastase
MMP-9 (92-kDa gelatinase, neutrophil gelatinase B or 92-kDa type 4 collagenase)
MMP-9 inhibitors
Eosinophils in interstitial lung disease
Mast cells in interstitial lung disease
LYMPHOCYTE ACTIVATION IN SYSTEMIC SCLEROSIS
Introduction
Circulating lymphocytes
Lymphocytes in interstitial lung disease
AIMS….

Source: Umea University

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