Angiotensin-Converting Enzyme Gene Does Not Contribute to Genetic Susceptibility to Systemic Sclerosis in European Caucasians

2009 ◽  
Vol 36 (2) ◽  
pp. 337-340 ◽  
Author(s):  
JULIEN WIPFF ◽  
GUILLAUME GALLIER ◽  
PHILIPPE DIEUDE ◽  
JEROME AVOUAC ◽  
KIET TIEV ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Angiotensin Converting Enzyme ◽  
Digital Ulcers ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Converting Enzyme ◽  
Combined Analysis ◽  
Genotype Frequencies ◽  
Pulmonary Arterial ◽  
Disease Haplotype

Objective.To determine whether angiotensin-converting enzyme (ACE) polymorphisms including I/D and 2 single-nucleotide polymorphisms (SNP) affect susceptibility to systemic sclerosis (SSc) in a large French Caucasian population.Methods.A case-control study was performed in 494 patients with SSc and 280 healthy controls for I/D polymorphism. Two supplementary exonic SNP of ACE gene (rs4309, rs4362) were genotyped in 659 patients with SSc and 511 matched healthy controls. Among the whole SSc population, 453 (67%) patients with SSc had the limited cutaneous subtype, 47 (7%) had precapillary pulmonary arterial hypertension, 209 (32%) had digital ulcers, and 10 (1.5%) had renal crisis. A combined analysis of the available results for ACE I/D genotypes in Caucasians was also performed.Results.There was no association between the 3 polymorphic markers and SSc for allelic and genotype frequencies. No association was observed for the different vascular subsets of the disease. Haplotype analyses did not detect any association. The lack of association for ACE I/D was confirmed by the combined analysis.Conclusion.These results in a large cohort of European Caucasian patients with SSc do not support that the ACE gene is implicated in the pathogenesis of SSc and its vascular damage.

scholarly journals AB0450 PERIPHERAL MACROVASCULAR INVOLVEMENT IN SYSTEMIC SCLEROSIS AS COMPARED WITH HEALTHY CONTROLS: A SMALL COHORT STUDY BY COLOR AND SPECTRAL DOPPLER ULTRASONOGRAPHY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1252.2-1252
Author(s):  
R. D’alessandro ◽  
E. Garcia Gonzales ◽  
P. Falsetti ◽  
C. Baldi ◽  
F. Bellisai ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Clinical Features ◽  
Doppler Ultrasonography ◽  
Power Doppler ◽  
Ulnar Artery ◽  
Artery Occlusion ◽  
Power Doppler Ultrasonography ◽  
Digital Ulcers ◽  
Healthy Controls ◽  
History Of

Background:Together with autoimmune-inflammation and fibrosis, microvasculopathy is a hallmark of SSc. However, also macrovascular changes may occur including peripheral proliferative vasculopathy. Whether this changes may represent a specific SSc marker with a predictive value remains a matter of debate.[1,2,3]Objectives:To study peripheral macrovascular involvement by color doppler ultrasound (CDUS) with spectral wave analysis (SWA) in a cohort of 40 SSc patients as compared to healthy controls. To further analyze any differences among the SSc population.Methods:Forty SSc patients and 36 healthy controls were examined by CDUS with SWA of both hands. Macrovascular involvement was assessed by measuring the resistivity index (RI) of distal ulnar and radial arteries. Examinations were performed with an Esaote MyLab Twice machine equipped with a linear 10-22 MHz probe. Ultrasound examination was carried out by two independent rheumatologists blinded to clinical conditions of the patients. Statistical analysis was performed by using MaxStat software.Results:The RI index resulted increased in the SSc cohort as compared with healthy controls (left ulnar RI 0.977 vs 0.715; right ulnar RI 0.996 vs 0.699; left radial RI 0.988 vs 0.706; right radial RI 0.999 vs 0.688; p<0.001). SSc patients with an increased RI in one artery were more probable to have an increased RI in the other vessels too (r 2 = 0.35; p<0.01). In addition, 8 out of 40 SSc patients presented left ulnar artery occlusion (UAO) and 7 out of 40 SSc patients presented right UAO, of which 6 presented bilateral UAO. Awaiting to enlarge the cohort for further analysis, descriptive data regarding increased RI at CDUS/SWA and clinical features, including years from onset of the disease, subtype of SSc, mRSS, history of digital ulcers, interstitial lung disease and PAH are described in Table 1.Conclusion:Peripheral macrovascular involvement was observed in SSc patients as compared with healthy controls. Further studies will determine whether this feature may have specificity for diagnosis/prognosis in SSc.References:[1]Lescoat A, Yelnik CM, Coiffier G et al. Ulnar Artery Occlusion and Severity Markers of Vasculopathy in Systemic Sclerosis: A Multicenter Cross-Sectional Study. Arthritis Rheumatol. 2019;71:983-990.[2]Lescoat A, Coiffier G, Rouil A et al. Vascular Evaluation of the Hand by Power Doppler Ultrasonography and New Predictive Markers of Ischemic Digital Ulcers in Systemic Sclerosis: Results of a Prospective Pilot Study. Arthritis Care Res (Hoboken). 2017;69:543-551.[3]Schioppo T, Orenti A, Boracchi P, De Lucia O, Murgo A, Ingegnoli F. Evidence of macro- and micro-angiopathy in scleroderma: An integrated approach combining 22-MHz power Doppler ultrasonography and video-capillaroscopy. Microvasc Res. 2019;122:125-130.Table 1.Main clinical features of the SSc cohort (n=40) studied by CDUS for macrovascular involvement.SSc cohort (n = 40)Years from onsetrange (35 y – 0 y)mean = 10.5 yAutoantibodiesACA 13/40Anti-TopoI 14/40Other 13/40mRSSrange (0 -30)mean = 3ILD17/40PAH7/40Capillaroscopy patternEarly 10/40Active 11/40Late 6/40History of digital ulcers16/40Left ulnar IR0.977Left radial IR0.988Right ulnar IR0.996Right radial IR0.999Disclosure of Interests:None declared.

scholarly journals Elite athletes and the gene for angiotensin-converting enzyme

1999 ◽  
Vol 87 (3) ◽  
pp. 1035-1037 ◽  
Author(s):  
Roger R. Taylor ◽  
Cyril D. S. Mamotte ◽  
Kieran Fallon ◽  
Frank M. van Bockxmeer
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Indirect Evidence ◽  
Cardiovascular Complications ◽  
Genotype Frequency ◽  
Community Control ◽  
Control Group ◽  
Converting Enzyme ◽  
Athletic Ability ◽  
Genotype Frequencies ◽  
Ace Genotype

The deletion (D) allele of the gene for angiotensin-converting enzyme (ACE) is associated with higher plasma and tissue levels of the enzyme and has also been related to a variety of cardiovascular complications, particularly myocardial infarction. On the basis of indirect evidence, we hypothesized that inheritance of the D allele would contribute to elite athletic ability. Over a period of 4 yr, 120 Caucasian athletes who were national (Australian) representatives in sports demanding a high level of aerobic fitness were recruited. Their ACE genotypes were compared with those of a community control group recruited randomly from the electoral roll. There was no difference in ACE genotype frequencies between the two groups. The DD genotype frequency was 30% in athletes and 29% in the control group, and the II genotype frequency was 22.5 and 22%, respectively. The results do not exclude the possibility that ACE genotype could be related to some attribute relating to a specific type of elite athletic ability or that there may be a difference between genders. Larger studies are desirable.

scholarly journals Capillaroscopy as an Outcome Measure for Clinical Trials on the Peripheral Vasculopathy in SSc—Is It Useful?

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Maurizio Cutolo ◽  
Alberto Sulli ◽  
Carmen Pizzorni ◽  
Vanessa Smith
Keyword(s):  
Clinical Trials ◽  
Systemic Sclerosis ◽  
Outcome Measure ◽  
Digital Ulcers ◽  
Nailfold Videocapillaroscopy ◽  
Therapeutic Trials ◽  
Specific Serum ◽  
Pulmonary Arterial ◽  
Microvascular Impairment ◽  
Clinical Conditions

Peripheral microvascular impairment in systemic sclerosis (SSc) may be easily detected and scored in a safe noninvasive way by nailfold videocapillaroscopy (NVC). The paper highlights clinical conditions related to SSc in which NVC may represent an outcome measure of therapeutical interventions, by elaborating on their already assessed relationship with the NVC patterns and eventually scores. The 3 important biological/clinical conditions are: the positivity for SSc-specific serum autoantibodies, the presence of SSc skin digital ulcers (DUs) and of pulmonary arterial hypertension (PAH) SSc associated. In conclusion, to the question if capillaroscopy (NVC) may represent in SSc an outcome measure for clinical trials on the peripheral vasculopathy, based on the growing evidence and our detailed studies, the answer is positive. Recent therapeutic trials in SSc are confirming this role, and the experience is growing rapidly.

scholarly journals Nailfold capillary density is associated with the presence and severity of pulmonary arterial hypertension in systemic sclerosis

2008 ◽  
Vol 68 (2) ◽  
pp. 191-195 ◽  
Author(s):  
H M A Hofstee ◽  
A Vonk Noordegraaf ◽  
A E Voskuyl ◽  
B A C Dijkmans ◽  
P E Postmus ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Capillary Density ◽  
Total Width ◽  
Healthy Controls ◽  
Mean Pulmonary Arterial Pressure ◽  
Microvascular Changes ◽  
Pulmonary Arterial ◽  
Disease Specificity

Objective:The aim of this study was to investigate whether there are differences in capillary nailfold changes in patients with systemic sclerosis (SSc) with and without pulmonary arterial hypertension (PAH), and whether these changes are associated with PAH severity and disease specificity.Methods:Capillary density and loop dimensions were studied in 21 healthy controls, 20 patients with idiopathic PAH (IPAH) and 40 patients with SSc. Of the 40 patients with SSc, 19 had no PAH (SSc–nonPAH) and 21 had PAH (SSc–PAH), of whom eight had PAH during exercise.Results:Capillary density was lower in SSc–PAH compared with patients who had SSc–nonPAH (4.33/mm vs 6.56/mm respectively, p = 0.001), but loop dimensions were equal. In comparison with IPAH, patients with SSc–PAH had reduced capillary density (4.33/mm vs 7.86/mm, p<0.001) and larger loop dimensions (total width 101.05 µm vs 44.43 µm, p<0.001). Capillary density in healthy controls (9.87/mm) was significantly higher when compared with SSc–nonPAH (6.56/mm), SSc–PAH (4.33/mm) and with IPAH (7.86/mm). No differences in capillary dimensions were present between healthy controls and IPAH.Capillary density correlated with mean pulmonary arterial pressure (PAP) at rest in SSc–PAH at rest (r = −0.58, p = 0.039) and IPAH (r = −0.67, p = 0.001).Conclusions:Reduction of nailfold capillary density, but not capillary loop dimensions is associated with PAH, and correlates with the severity of PAH in both SSc and IPAH. This suggests that either systemic microvascular changes play a part in the development of PAH, or that PAH itself contributes to systemic microvascular changes.

scholarly journals A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension

2018 ◽  
Vol 51 (6) ◽  
pp. 1702638 ◽  
Author(s):  
Anna R. Hemnes ◽  
Anandharajan Rathinasabapathy ◽  
Eric A. Austin ◽  
Evan L. Brittain ◽  
Erica J. Carrier ◽  
...  
Keyword(s):  
Pilot Study ◽  
Pulmonary Arterial Hypertension ◽  
Angiotensin Converting Enzyme ◽  
Arterial Hypertension ◽  
Pulmonary Arteries ◽  
Converting Enzyme ◽  
Open Label ◽  
Angiotensin Converting Enzyme 2 ◽  
Markers Of Inflammation ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a deadly disease with no cure. Alternate conversion of angiotensin II (AngII) to angiotensin-(1–7) (Ang-(1–7)) by angiotensin-converting enzyme 2 (ACE2) resulting in Mas receptor (Mas1) activation improves rodent models of PAH. Effects of recombinant human (rh) ACE2 in human PAH are unknown. Our objective was to determine the effects of rhACE2 in PAH.We defined the molecular effects of Mas1 activation using porcine pulmonary arteries, measured AngII/Ang-(1–7) levels in human PAH and conducted a phase IIa, open-label pilot study of a single infusion of rhACE2 (GSK2586881, 0.2 or 0.4 mg·kg−1 intravenously).Superoxide dismutase 2 (SOD2) and inflammatory gene expression were identified as markers of Mas1 activation. After confirming reduced plasma ACE2 activity in human PAH, five patients were enrolled in the trial. GSK2586881 was well tolerated with significant improvement in cardiac output and pulmonary vascular resistance. GSK2586881 infusion was associated with reduced plasma markers of inflammation within 2–4 h and increased SOD2 plasma protein at 2 weeks.PAH is characterised by reduced ACE2 activity. Augmentation of ACE2 in a pilot study was well tolerated, associated with improved pulmonary haemodynamics and reduced markers of oxidant and inflammatory mediators. Targeting this pathway may be beneficial in human PAH.

scholarly journals Uremic Apelin and Leucocytic Angiotensin-Converting Enzyme 2 in CKD Patients

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 742
Author(s):  
Bogusz Trojanowicz ◽  
Christof Ulrich ◽  
Matthias Girndt
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Healthy Controls ◽  
Converting Enzyme ◽  
Blood Pressure Lowering ◽  
Angiotensin Converting Enzyme 2 ◽  
Pressure Lowering ◽  
The Impact ◽  
Progression Of Atherosclerosis

Apelin peptides (APLN) serve as second substrates for angiotensin-converting enzyme 2 (ACE2) and, in contrast to angiotensin II (AngII), exert blood-pressure lowering and vasodilatation effects through binding to G-coupled APLN receptor (APLNR). ACE2-mediated cleavage of the APLN may reduce its vasodilatory effects, but decreased ACE2 may potentiate the hypotensive properties of APLN. The role of APLN in uremia is unclear. We investigated the correlations between serum-APLN, leucocytic APLNR, and ACE2 in 32 healthy controls (NP), 66 HD, and 24 CKD3–5 patients, and the impact of APLN peptides on monocytic behavior and ACE2 expression under uremic conditions in vitro. We observed that serum APLN and leucocytic APLNR or SLCO2B1 were significantly elevated in uremic patients and correlated with decreased ACE2 on uremic leucocytes. APLN-treated THP-1 monocytes revealed significantly increased APLNR and ACE2, and reduced TNFa, IL-6, and MCSF. Uremic toxins induced a dramatic increase of miR-421 followed by significant reduction of ACE2 transcripts, partially counteracted with APLN-13 and -36. APLN-36 triggered the most potent transmigration and reduction of endothelial adhesion. These results suggest that although APLN peptides may partly protect against the decay of monocytic ACE2 transcripts, uremic milieu is the most dominant modulator of local ACE2, and likely to contribute to the progression of atherosclerosis.

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