Brachial Artery Endothelial-dependent Flow-mediated Dilation Identifies Early-stage Endothelial Dysfunction in Systemic Sclerosis and Correlates with Nailfold Microvascular Impairment

Rollando, Daniela; Bezante, Gian Paolo; Sulli, Alberto; Balbi, Manrico; Panico, Nicoletta; Pizzorni, Carmen; Negrini, Simone; Brunelli, Claudio; Barsotti, Antonio; Cutolo, Maurizio; Indiveri, Francesco; Ghio, Massimo

doi:10.3899/jrheum.091116

Cited by 52 publications

(43 citation statements)

References 24 publications

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“…Another study showed that flowmediated dilatation was decreased in patients with SSc compared with controls (8). Some studies found nitratemediated dilatation was reduced in SSc, suggesting coexisting functional or structural abnormalities of arterial smooth muscle, adventitia, or both (48,49). Our patient cohort had an impaired CFR with increased ADMA levels.…”

Section: Discussionmentioning

confidence: 81%

“…Among the noninvasive techniques, echocardiography with CFR assessment plays the most important role, as has been reported in a recent review undertaken by the University of California (46). However, endothelial dysfunction has been assessed using flow-mediated dilatation (47,48). Another study showed that flowmediated dilatation was decreased in patients with SSc compared with controls (8).…”

Section: Discussionmentioning

confidence: 96%

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Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross‐sectional study

Turiel¹,

Gianturco²,

Ricci³

et al. 2013

Arthritis Care & Research

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Objective. An association between systemic autoimmune diseases and atherosclerosis has been described in many connective tissue diseases, and this association is known to lead to increased cardiovascular morbidity and mortality. Systemic sclerosis (SSc) is characterized by multisystem organ inflammation, endothelial wall damage, and vasculopathy. There are many markers of endothelial dysfunction and/or atherosclerotic risk, such as asymmetric dimethylarginine (ADMA), arterial stiffness parameters, carotid intima-media thickness (CIMT), and coronary flow reserve (CFR) assessed by transthoracic echocardiography. The aim of this pilot study was to use various endothelial and atherosclerosis markers to identify early cardiovascular involvement in a group of SSc patients. Methods. The study involved 20 patients (2 men and 18 women with a mean ؎ SD age of 52.96 ؎ 12.51 years) with diffuse SSc who had no signs or symptoms of cardiovascular disease (CVD) and 20 age-and sex-matched controls. All subjects underwent a dipyridamole echocardiographic stress test that included a determination of CFR and an evaluation of CIMT, arterial stiffness, and plasma ADMA levels. Results. All of the arterial wall measurements of the patients with diffuse SSc were significantly different from those of the controls, and both right and left CIMT, pulse wave velocity, and stiffness index (␤) were significantly elevated in the SSc patients compared to the healthy controls. Moreover, in patients with diffuse SSc, CFR was significantly lower (P ‫؍‬ 0.0033) and plasma ADMA levels were higher (P < 0.0001) than in healthy controls. Conclusion. SSc patients without any clinical evidence of CVD seem to have had subclinical atherosclerosis, which was suggested by early impairment of coronary microcirculation and macrovascular involvement.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 96%

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross‐sectional study

Turiel¹,

Gianturco²,

Ricci³

et al. 2013

Arthritis Care & Research

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“…Since calcification and fibrosis reduce vascular compliance and subsequently affect NO signaling by limiting vascular stretch [72,73], vascular stiffness itself is also an important factor determining FMD. In SSc patients, several studies have demonstrated the reduction of FMD values [74][75][76][77][78][79][80][81]. More importantly, the inverse correlation of FMD values with pulmonary arterial pressure and the association of decreased FMD values with the presence of PAH and digital ulcers have been reported [12,79].…”

Section: Endothelial Dysfunction In Sscmentioning

confidence: 96%

Vasculopathy in scleroderma

2015

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Systemic sclerosis (SSc) is a multisystem connective tissue disorder featured by vascular injury and fibrosis of the skin and various internal organs with autoimmune background. Although the pathogenesis of SSc still remains elusive, it is generally accepted that initial vascular injury due to autoimmunity and/or environmental factors causes structural and functional abnormalities of vasculature which eventually result in the constitutive activation of fibroblasts in various organs. Structural alterations consist of destructive vasculopathy (loss of small vessels) and proliferative obliterative vasculopathy (occlusion of arterioles and small arteries with fibro-proliferative change) caused by impaired compensatory vasculogenesis and angiogenesis. Impaired function of SSc vasculature includes the altered expression of cell adhesion molecules predominantly inducing Th2 and Th17 cell infiltration, endothelial dysfunction primarily due to the low availability of nitric oxide, the activated endothelial-to-mesenchymal transition leading to fibro-proliferative vascular change and tissue fibrosis, and the impaired coagulation/fibrinolysis system promoting the formation of intravascular fibrin deposits. Recent new insights into the therapeutic mechanisms of intravenous cyclophosphamide pulse and bosentan and the establishment of a new SSc animal model (Klf5 (+/-);Fli1 (+/-) mice) provide us useful clues to further understand the development of vascular alterations characteristic of SSc. This article overviewed the present understanding of the pathogenesis of SSc vasculopathy.

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“…The increase observed in the BA diameter is an indirect measure of NO release, and, thus, of endothelium-dependent vasodilation. 15 A small percentage fl ow increase mediated by endotheliumdependent vasodilation can be interpreted as low availability of NO, being associated with an increased risk for vascular disease. 16 The defi cient endothelium-dependent vasodilation found in SSc can be explained by lack of production and release of vasodilating substances by the chronically injured endothelium, especially NO, while normal vasodilating response to endothelium-independent factors (exogenous nitroglycerin) can be observed.…”

Section: Introductionmentioning

confidence: 99%

Avaliação da função endotelial em pacientes com esclerose sistêmica limitada por meio do eco Doppler da artéria braquial

Fernandes¹,

Bica²,

Villela³

et al. 2012

Rev. Bras. Reumatol.

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Objectives: The aim of this study was to compare the brachial artery endothelium-dependent and endothelium-independent dilating responses in patients with limited systemic sclerosis (LSSc) with those of healthy subjects of the same gender, age and color. Methods: Twenty adult, non-obese, non-smoker, non-diabetic, non-dyslipidemic, and non-hypertensive women, who fulfi lled the American College of Rheumatology criteria for the diagnosis of SSc, were submitted to right brachial artery Doppler ultrasound. The vasodilating responses were analyzed as follows: the endothelium-dependent dilating response, after a 5-minute ischemia in the right arm; and the endothelium-independent dilating response, after administering 300 mcg of nitroglycerin (NTG) sublingually. The results were compared with the response obtained in healthy subjects. Results: Brachial artery longitudinal diameter was signifi cantly low at baseline 1: 3.57 ± 0.52 mm and 3.93 ± 0.39 mm for the LSSc group and the control group, respectively, P = 0.005. The vascular reactivity after the ischemia/reactive hyperemia and the NTG showed no signifi cant difference between the groups (8.60 ± 5.45 mm vs. 9.26 ± 5.91 mm and 25.01 ± 12.55 mm vs. 19.59 ± 7.94 mm for the LSSc and control groups, respectively). Also, no statistically signifi cant difference was found between red blood cell velocity (RBCV) after reactive hyperemia and NTG (110.2 ± 43.86 cm/s vs. 102.0 ± 25.89 cm/s and 63.80 ± 17.69 cm/s vs. 65.4 ± 12.90 cm/s in the LSSc and control groups, respectively). Conclusion: Although the LSSc group showed lower brachial artery diameter, the endotheliumdependent and the endothelium-independent dilating responses were preserved in both groups.

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Brachial Artery Endothelial-dependent Flow-mediated Dilation Identifies Early-stage Endothelial Dysfunction in Systemic Sclerosis and Correlates with Nailfold Microvascular Impairment

Abstract: We demonstrated the simultaneous presence of macrovascular and microvascular impairment in patients with SSc, which was already present in the early phase of the vascular disease.

Cited by 52 publications

References 24 publications

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross‐sectional study

Silent cardiovascular involvement in patients with diffuse systemic sclerosis: a controlled cross‐sectional study

Vasculopathy in scleroderma

Avaliação da função endotelial em pacientes com esclerose sistêmica limitada por meio do eco Doppler da artéria braquial

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