angiotensin-i and Scleroderma--Systemic

Systemic sclerosis (SSc) is a multisystemic disease with an extensive microvasculopathy. Previously, disturbances in plasma levels of angiotensin II (Ang II) and its antagonistic angiotensin-(1-7) (Ang-(1-7)) were found in patients with SSc. Their significance in a pathogenesis of SSc stays unclear due to discrepancies of earlier studies.. To evaluate a significance of disturbances in production pathway of angiotensins in a development of SSc.. There were enrolled 27 patients with established SSc, 23 subjects with very early SSc and 23 healthy controls. The diagnosis of SSc was established in patients who met EULAR/ACR 2013 classification criteria. Very early SSc described patients with Raynaud's phenomenon having SSc-specific antinuclear antibodies and SSc-like abnormalities in nailfold videocapillaroscopy. Patients were submitted to evaluation of internal organ involvement and blood sampling to assay plasma levels of angiotensin I, angiotensin II and angiotensin-(1-7) with ELISA technique.. Plasma level of angiotensin-(1-7) was significantly reduced in both SSc group (median = 47.2 pg/mL; P < 0.001) and ones with very early SSc (median = 102.7 pg/mL; P = 0.002) when compared to healthy controls (median = 176.1 pg/mL). A tendency to higher than in control group (median = 214 pg/mL) plasma level of angiotensin I was seen in SSc group (median = 392 pg/mL; P = 0.059). Differences in plasma level of angiotensin II were insignificant between all study groups. Those disturbances produced unfavourable angiotensin-(1-7)/angiotensin II (%) ratio in both groups of patients, which achieved statistical significance in subjects with established SSc (P < 0.001). Production pathway of angiotensins showed a dependence on a subtype of SSc, immune profile and a presence of interstitial lung disease.. Production of angiotensin-(1-7) was significantly reduced in both SSc patients and those ones with very early SSc, although a significant imbalance between angiotensin II and angiotensin-(1-7) occurred only in subjects with established disease.

Topics: Adult; Aged; Angiotensin I; Angiotensin II; Female; Humans; Male; Middle Aged; Peptide Fragments; Scleroderma, Systemic; Young Adult

Traditionally viewed as important in the regulation of blood pressure, the renin-angiotensin system--and specifically the angiotensin-converting enzyme (ACE)-angiotensin (Ang) II-AT1 receptor axis--may play a prominent role to promote inflammation and fibrosis. ACE2, a new component of the renin-angiotensin system, has emerged as a key enzyme that selectively degrades Ang II and generates Ang-(1-7), a bioactive peptide with anti-inflammatory and anti-fibrotic actions. Takahashi and colleagues demonstrate circulating titers of inhibitory autoantibodies against ACE2 in patients with systemic sclerosis. The current study reveals a potentially novel mechanism to attenuate the catalytic activity of ACE2, thereby promoting the actions of Ang II.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Autoantibodies; Humans; Hypertension; Peptide Fragments; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Scleroderma, Systemic

Systemic sclerosis (SSc) impairs endothelium-dependent vasodilatation. Among angiotensin I (Ang I)-derived compounds, vasoconstrictor angiotensin II (Ang II) and vasodilator angiotensin-(1-7) (Ang-(1-7)), cleaved from ACE and neutral endopeptidase (NEP) 24.11, respectively, play an important role in vascular tone regulation. Ang-(1-7) may act independently or by activating other vasodilating molecules, such as nitric oxide (NO) or prostaglandin I2 (PGI2). Our aim was to assess, in patients with SSc, circulating levels of Ang I, Ang II and Ang-(1-7), with their metabolising enzymes ACE and NEP, and levels of NO and PGI2, and to correlate them to the main characteristics of SSc.. Levels of Ang I, Ang II, Ang-(1-7), NEP, ACE, NO and PGI2 were measured in 32 patients with SSc, who were also assessed for humoral and clinical characteristics, and 55 controls.. Plasma Ang I, Ang II and Ang-(1-7) levels were lower in patients with SSc than in controls (p<0.001in all cases). When Ang II and Ang-(1-7) levels were expressed as a function of the available Ang I, lower Ang-(1-7) levels in patients with SSc than in controls were confirmed (p<0.001), while no difference was found for Ang II levels. In patients with SSc, the Ang II/Ang-(1-7) ratio indicated a prevalence of Ang II over Ang-(1-7), while in controls Ang-(1-7) was prevalent (p<0.001). Levels of ACE, NEP, NO and PGI2 were lower in patients with SSc than in controls (p<0.05 in all cases).. In patients with SSc, prevalence of the vasoconstricting Ang II over the vasodilator Ang-(1-7) suggests a dysfunction of the angiotensin-derived cascade that may contribute to dysregulation of vascular tone.

Topics: Angiotensin I; Angiotensin II; Antihypertensive Agents; Epoprostenol; Female; Humans; Male; Middle Aged; Neprilysin; Nitric Oxide; Peptide Fragments; Peptidyl-Dipeptidase A; Scleroderma, Systemic; Vasoconstrictor Agents