T-Lymphocyte-Based Renin Angiotensin System in Obesity

Abstract

Obesity can be associated with increased cardio-metabolic risk, but some subjects with obesity do not show metabolic impairment and escape this association. Low-grade inflammation (i.e., high sensitivity C-reactive protein [hsCRP] > 3 mg/dL) is associated with high cardiovascular risk in obesity. We investigated renin-angiotensin system (RAS) activity in cultured circulating T-cells in subjects with obesity with and without angiotensin II (Ang II) stimulation in the presence or absence of low-grade inflammation. We studied 18 subjects with obesity and 10 healthy subjects. After T-lymphocyte isolation, T-cell mRNAs for angiotensin converting enzyme (ACE) and AT1-receptor were quantified by reverse transcription polymerase chain reaction at baseline and after Ang II stimulation. hsCRP, plasma renin and ACE activity in the cell pellet and supernatant and Ang II T-cell content were also measured. T-cell RAS in subjects with obesity with low-grade inflammation was more activated than in subjects with obesity without low-grade inflammation. The increase in RAS activation occurred both at baseline and after Ang II stimulation. Similarly, the release of ACE activity in the supernatant was significantly higher in subjects with obesity with hsCRP > 3 mg/dL than in subjects with hsCRP < 3 mg/dL and controls. Circulating T-cell based RAS is activated in subjects with obesity independently of low-grade inflammation that amplifies the T-cell RAS response to Ang II stimulation.