Lack of efficacy of quinapril on vascular damage in limited cutaneous systemic sclerosis

2008 ◽  
Vol 4 (6) ◽  
pp. 288-289 ◽  
Author(s):  
Serena Guiducci ◽  
Marco Matucci Cerinic
Keyword(s):  
Systemic Sclerosis ◽  
Vascular Damage

scholarly journals Apoptosis Modulation as a Promising Target for Treatment of Systemic Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Stéphane Chabaud ◽  
Véronique J. Moulin
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Disease ◽  
Therapeutic Targets ◽  
Immune Dysfunction ◽  
Vascular Damage ◽  
Loss Of Function ◽  
Internal Organs ◽  
Promising Target ◽  
New Findings ◽  
Diffuse Systemic Sclerosis

Diffuse systemic sclerosis (SSc) is a fatal autoimmune disease characterized by an excessive ECM deposition inducing a loss of function of skin and internal organs. Apoptosis is a key mechanism involved in all the stages of the disease: vascular damage, immune dysfunction, and fibrosis. The purpose of this paper is to gather new findings in apoptosis related to SSc, to highlight relations between apoptosis and fibrosis, and to identify new therapeutic targets.

scholarly journals P169 Analysis of left ventricle dysfunction, pulmonary disease and nailfold videocapillaroscopy patterns in asymptomatic patients with early systemic sclerosis

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Francesco Masini ◽  
Lucio Monaco ◽  
Klodian Gjeloshi ◽  
Emanuele Pinotti ◽  
Roberta Ferrara ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Pulmonary Function ◽  
Diastolic Dysfunction ◽  
Pulmonary Function Tests ◽  
Vascular Damage ◽  
Nailfold Videocapillaroscopy ◽  
Microvascular Damage ◽  
Function Tests ◽  
Asymptomatic Patients

Abstract Background Systemic sclerosis (SSc) is a multi-system connective tissue disease characterized by microvascular damage, inflammation and fibrosis. The aim of our study is to investigate a possible correlation between nailfold videocapillaroscopy patterns and internal organ involvement in patients with early SSc. Methods We enrolled 40 patients with early SSc according to LeRoy criteria and performed echocardiogram, pulmonary function tests (PFTs) and nailfold videocapillaroscopy. Results 20 patients had early pattern and 20 active pattern. A comparative analysis between SSc patients and healthy controls showed an alteration of mitral annular plane systolic excursion (MAPSE) (1.5±0.1 vs 1.7±0.1; p < 0.001), respectively; an increased occurrence of diastolic dysfunction (11/40 vs 0/21; p = 0.01) respectively; a higher values of systolic pulmonary arterial pression (PAPs) (32±6 vs 22±6; p < 0.001) and a higher frequency of patients with pulmonary hypertension (12/40 vs 0/21; p = 0.005) in SSc group. The patients with an active capillaroscopic pattern showed a trend of reduction in MAPSE, diastolic dysfunction, contractility of the right ventricle and pulmonary function tests parameters. We observed a correlation between myocardial and pulmonary vascular damage and between myocardial and pulmonary fibrosis, with lower DLCO value in patients with diastolic dysfunction (64±17 vs 85±9; p < 0.0001). Conclusion A subclinical myocardial damage in these patients may be observed also in the absence of symptoms. In fact, in our study it can be noted that asymptomatic patients present a reduction in the linear myocardial contractility. Furthermore, we observed the presence of grade I diastolic dysfunction in 27.5% of cases, a sign of an initial stiffening of the wall, likely due to a fibrotic damage. In our study linear contractility emerges to be not correlated with the presence of diastolic dysfunction. Such data is very intriguing if we consider that in many studies the resolution of linear contractility with conserved ejection fraction correlated with subendocardial damage induced by microcirculation alterations. The hypothesis is the presence of a double framework at the myocardial level: a vascular damage and the presence of increased inflammation and fibrosis. The presence fibrosis is correlated between the various organs, with the values of DLCO strongly correlating with the presence of diastolic dysfunction; instead DLCO values do not correlate with pulmonary pressure values. The analysis of the capillaroscopic parameters we observed how in the early pattern the presence of vascular damage with MAPSE and PAPs alterations and presence of pulmonary hypertension emerge, while passing from early to active the presence of fibrotic damage becomes evident, the diastolic dysfunction passing from 15% to 40% and DLCO passing from 83% to 75%. The presence of subclinical cardiac and pulmonary damage in patients with systemic sclerosis and that this damage is closely related to the capillaroscopic pattern. Disclosures F. Masini: None. L. Monaco: None. K. Gjeloshi: None. E. Pinotti: None. R. Ferrara: None. T. Salvatore: None. G. Cuomo: None.

scholarly journals Sildenafil Reduces Expression and Release of IL-6 and IL-8 Induced by Reactive Oxygen Species in Systemic Sclerosis Fibroblasts

2020 ◽  
Vol 21 (9) ◽  
pp. 3161 ◽  
Author(s):  
Luigi Di Luigi ◽  
Paolo Sgrò ◽  
Guglielmo Duranti ◽  
Stefania Sabatini ◽  
Daniela Caporossi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Systemic Sclerosis ◽  
Tissue Damage ◽  
Human Fibroblasts ◽  
Reactive Oxygen ◽  
Dermal Fibroblasts ◽  
Vascular Damage ◽  
Oxygen Species ◽  
Phosphodiesterase Type 5 Inhibitor

Oxidative stress linked to vascular damage plays an important role in the pathogenesis of systemic sclerosis (SSc). Indeed, vascular damage at nailfold capillaroscopy in patients with Raynaud’s Phenomenon (RP) is a major risk factor for the development of SSc together with the presence of specific autoantiobodies. Here, we investigated the effects of the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil, currently used in the management of RP, in modulating the proinflammatory response of dermal fibroblasts to oxidative stress in vitro. Human fibroblasts isolated from SSc patients and healthy controls were exposed to exogenous reactive oxygen species (ROS) (100 µM H2O2), in the presence or absence of sildenafil (1 µM). Treatment with sildenafil significantly reduced dermal fibroblast gene expression and cellular release of IL-6, known to play a central role in the pathogenesis of tissue damage in SSc and IL-8, directly induced by ROS. This reduction was associated with suppression of STAT3-, ERK-, NF-κB-, and PKB/AKT-dependent pathways. Our findings support the notion that the employment of PDE5i in the management of RP may be explored for its efficacy in modulating the oxidative stress-induced proinflammatory activation of dermal fibroblasts in vivo and may ultimately aid in the prevention of tissue damage caused by SSc.

Vascular damage and lack of angiogenesis in systemic sclerosis skin

2003 ◽  
Vol 22 (3) ◽  
pp. 196-202 ◽  
Author(s):  
Y.T. Konttinen ◽  
Z. Mackiewicz ◽  
P. Ruuttila ◽  
A. Ceponis ◽  
A. Sukura ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Vascular Damage

scholarly journals Anti-Annexin V Antibodies: Association with Vascular Involvement and Disease Outcome in Patients with Systemic Sclerosis

2010 ◽  
Vol 3 ◽  
pp. CMAMD.S4503 ◽  
Author(s):  
Reem A. Habeeb ◽  
Howaida E. Mansour ◽  
Aya M. Abdeldayem ◽  
Rania A. Abo-Shady ◽  
Iman A. Hassan ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Significant Positive Correlation ◽  
Disease Activity Score ◽  
Resistive Index ◽  
Annexin V ◽  
Anticardiolipin Antibodies ◽  
Vascular Damage ◽  
Vascular Involvement ◽  
Positive Correlation ◽  
Main Renal Artery

Background Systemic Sclerosis (SSc) is characterized by skin thickening, fibrosis and vascular obliteration. The onset and course are heterogeneous. Prominent features include autoimmunity, inflammation and vascular damage. Aim of Study To measure the level of serum Anti-Annexin V antibodies in SSc patients and to study its significance in relation to vascular damage in these patients. Patients and Methods Twenty patients with SSc (12 with diffuse SSc and 8 with the limited form) and 10 healthy age and sex matched volunteers as controls were all subjected to routine laboratory testing and immunological profiling including antinuclear, anti-Scl-70, anticentomere, anticardiolipin antibodies and anti-annexin V antibodies titres. Vascular damage was assessed by clinical examination and assessment of the disease activity score, nailfold capillaroscopy and colour flow Doppler of the renal arteries; Doppler echocardiography was used for assessing pulmonary hypertension. Results Anti-annexin V antibodies were detected in 75% of patients. Comparisons between anti-annexin V in diffuse and limited subgroups showed no significance; however a statistically significant positive correlation was found between Anti-annexin V titre and the degree of vascular damage in SSc patients. Anti-annexin V increased significantly in patients with severe vascular damage in comparison with those less affected (15.3 ± 6.6 vs. 11.25 ± 3.6, P < 0.05). A significant positive correlation was found between Anti-annexin V titre and both the ACL titre (r = 0.79, P < 0.001) and the resistive index of the main renal artery (r = 0.42, P < 0.05). Conclusion Anti-annexin V antibodies were significantly present in sera of patients with SSc. Patients with more severe forms of vascular damage had higher titres of these antibodies. Anti-annexin V antibodies are a sensitive predictor of vascular damage in SSc and could serve as a useful parameter in discriminating patients with a higher risk of vascular affection from those without.

scholarly journals Mechanisms of vascular damage in systemic sclerosis

Autoimmunity ◽  
2009 ◽  
Vol 42 (7) ◽  
pp. 587-595 ◽  
Author(s):  
Ulf Müller-Ladner ◽  
Oliver Distler ◽  
Lidia Ibba-Manneschi ◽  
Elena Neumann ◽  
Steffen Gay
Keyword(s):  
Systemic Sclerosis ◽  
Vascular Damage
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