Statistical significance was taken as em P /em 0

Statistical significance was taken as em P /em 0.05 for all those calculations. Results PRA and hs-CRP in controls, stable and unstable angina patients In control subjects, PRA in venous blood was 10.51.5 pmol/L per minute (range 4.5C15.2 pmol/L per minute). unstable angina patients than in T cells from stable angina patients and controls, and further increased after angiotensin II addition to cultured T Rabbit Polyclonal to DBF4 cells. ACE activity of unstable angina T cells was significantly higher than that of T cells from controls and stable angina patients. Only in T cells from unstable angina patients did angiotensin II stimulation cause the almost complete release of ACE activity in the supernatant. Conclusions: The circulating T-cell-based reninCangiotensin system from unstable angina BIO-5192 patients was selectively upregulated. In vivo unstable angina T cells could locally increase angiotensin II concentration in tissues where they migrate independently of the circulating reninCangiotensin system. strong class=”kwd-title” Keywords: Angiotensin-converting enzyme, angiotensin II, T cell, unstable angina, reninCangiotensin system Introduction The reninCangiotensin system (RAS) is well known to play an important role in the initiation and amplification of atherosclerosis damage that clinically results in cardiovascular disease. In previous studies1 we exhibited that in patients with unstable angina the cardiac RAS is usually activated and sustains an increased de novo production of cardiac angiotensin (Ang) II. Upregulated cardiac RAS participates in the coronary microvessel inflammation of unstable angina and strengthens the immunomediated component of myocardial inflammation. Indeed, in unstable angina myocardium-positive immunostaining for angiotensin-converting enzyme (ACE) co-localised with T cells and endothelial BIO-5192 cells. In agreement with this obtaining, experimental and human studies showed that Ang II may be produced by T cells that are fully equipped with RAS components and specifically can express the gene for key components of the RAS, such as ACE and angiotensinogen.2C4 According to these findings, BIO-5192 Ang II acts on and is produced by inflammatory cells,5 can affect T-cell behaviour by angiotensin type 1 receptor (AT1-R) and induce cellular interferon-gamma (IFN-) secretion and interleukin 2 production.6 T-cell RAS is functionally autonomous from circulating and various tissue-based RAS and can synthesise Ang II that acts as a positive feedback loop on inflammatory cells to amplify the inflammatory reaction further.7C9 In our previous paper we showed that in hypertensive patients with low grade inflammation the T-cell RAS response to Ang II is amplified in comparison with T cells from controls and hypertensive individuals without inflammation. Our findings gave strong support to the hypothesis that T-cell RAS activity was strictly related to inflammatory lymphocyte activation. In unstable angina patients, circulating T cells are activated and sustain the acute systemic inflammation that precipitates plaque instability. Serum high-sensitivity C-reactive protein (hs-CRP) is usually a sensitive indicator of inflammation, which is usually closely related to the BIO-5192 progress of plaque and markedly increases in acute coronary syndrome (ACS). The increase in hs-CRP is usually slight or absent in patients with stable coronary plaques. Up to now, no data are available about the behaviour of circulating T-cell RAS of patients with ACS or stable angina. This study was aimed at investigating whether an activation of cell-based RAS could be present in circulating T cells from patients with unstable or stable angina with increased or normal hs-CPR levels. We also investigated whether in vitro the addition of Ang II could stimulate or inhibit cultured T-cell RAS from unstable or stable angina patients. Materials and methods BIO-5192 We examined 13 patients with unstable angina in classes IIB ( em n /em =5) and IIIB ( em n /em =8) and 10 patients with stable angina in Canadian classes II ( em n /em =4) and III ( em n /em =6), who had been admitted to the cardiological intensive therapy unit of Careggi Teaching Hospital, Florence, Italy. We excluded those patients on ACE inhibitors and/or Ang II receptor antagonists and those with acute or chronic diseases accompanied by evidence of circulating RAS activation. Ten subjects in apparent good health comparable for age and sex to unstable and stable angina patients formed the control group. The protocol of the study complies with the theory of the Helsinki declaration and was approved by the ethical.