CARDIOVASCULAR RISK, METABOLIC PROFILE AND INFLAMMATORY FINGERPRINT OF OBESE SUBJECTS UNDERGOING BARIATRIC SURGERY

Abstract

Objective: Bariatric surgery has emerged as effective treatment for obesity not only for the substantial and durable weight loss, but also by improving several obesity-related comorbidities, including hypertension. Extracellular vesicles (EVs; membrane nanoparticles released by cells) and their cargo reflect endothelial dysfunction and inflammation, and may be used as indicators of post-surgical outcomes in these patients. The aim of the present study was to exploit an EV signature to assess cardiovascular (CV) risk, metabolic profile, and inflammatory fingerprint before and after bariatric surgery. Design and method: The study cohort was composed by 62 patients (age 39 years; 21% males); for each subject, clinical and biochemical parameters, disease status (including diabetes, dyslipidemia, and hypertension), medications, and EV profiling were evaluated at baseline (T0) and 1-/3-years (T1 and T2, respectively), after surgery (sleeve gastrectomy or Roux-en-Y gastric bypass). EVs were isolated from serum by beads-based immuno-capture and analyzed for the expression of 37 membrane-associated antigens. Results: After bariatric surgery, patients gradually lost weight from a median of 110 Kg at T0 down to 80 Kg at T2 (cumulative weight loss 31 Kg; 29.9% BMI reduction). Accordingly, the overall CV risk and metabolic-inflammatory profile of patients improved: systolic blood pressure, HbA1c, total cholesterol, triglycerides, LDL, uric acid, white blood cells, and C-reactive protein decreased, while HDL and renal function (expressed as eGFR) increased at follow-up (p < 0.05 for all comparisons); prevalence of hypertension, dyslipidemia, and diabetes decreased together with the number of assumed drugs (anti-hypertensives, statins, hypoglycemic, and anti-platelets agents). Consistently, levels of expression of EV specific markers (CD9-CD63-CD81) and 11 out of the 37 evaluated antigens (mainly from endothelium, platelets, and inflammatory cells) decreased at T1/T2, reflecting changes of main CV risk indicators. Interestingly, lower baseline levels of CD4, CD31, CD40, CD42a, and CD62P were associated to a complete post-surgical outcome, defined as no residual disease without medications, with a BMI at T2 lower than 30 Kg/sqm. Conclusions: EV-derived biomarkers reflect the improvement of CV profile in patients who underwent bariatric surgery and may become a new tool to predict post-surgical outcome.