ஜர்னல் ஆஃப் கிளினிக்கல் அண்ட் செல்லுலார் இம்யூனாலஜி
திறந்த அணுகல்

சுருக்கம்

Up-regulated Circulating T-cell Angiotensin Converting Enzyme Gene Expression and Activity in Acute Coronary Syndromes

Coppo M, Bandinelli M, Poggesi L, and Boddi M

Background: T-cells are endowed with a functional cell-based renin angiotensin system (RAS), related with and independent by circulating RAS that can autonomously synthesize angiotensin (Ang) II. Angiotensing converting enzyme (ACE) is the key step for the regulation of the synthesis of Ang II by RAS and T-cell ACE gene expression was reported to be up-regulated in hypertensives with low grade inflammation. Ang II and T-cells play a major role in the systemic inflammation that occurs in unstable angina patients, but whether T-cell based RAS is directly involved is unknown.

This study was aimed at measuring ACE gene expression and enzymatic activity in the cell pellet and in the supernatant of human cultured circulating T-cells obtained from control subjects, hypertensive or unstable angina patients. C reactive protein (CRP) levels as a marker of systemic inflammation were also investigated.

Methods: mRNA for ACE gene expression was obtained in T cells isolated from peripheral blood and quantified by real time transcriptase–polymerase chain reaction (PCR); mRNAs for INF-gamma was semi-quantified versus the housekeeping gene glyceraldeyde-3-phosphate dehydrogenase (GAPDH) by reverse transcriptase (RT) PCR. ACE activity in cell pellet and in the culture medium (supernatant) was measured by the high performance liquid chromatography (HPLC) assay of a synthetic substrate. Plasma renin activity (PRA) and Ang II levels were measured by radioimmunoassay and high sensitive C Reactive Protein (hsCRP) by a commercial kit.

Results: In hypertensive and more markedly in anginal patients increased mRNA levels for ACE, augmented cell-based ACE enzymatic activity and Ang II levels were measured in cultured circulating T-cells when compared with data obtained in T cells from controls (p<0.05 for alls). The addition of Ang II to the T-cell pellet further increase ACE activity and Ang II synthesis. In anginal patients who showed the highest ACE gene expression and enzymatic activity and hsCRP values, Ang II stimulation of T-cells induced an almost complete release of ACE in the supernatant.

Conclusions: In anginal patients with hsCRP levels >3 mg/dl a marked up-regulation of circulating T-cell-based ACE gene expression and activity did occur in T-cell culture, further amplified by Ang II. According to our in vitro findings, in vivo activated T-cells could autonomously increase local de novo Ang II synthesis in tissues where they migrate and play a role in coronary plaque rupture and microvessel damage of unstable angina.