Nitrate treatment decreases circulating matrix metalloproteinases concentrations in overweight women

Nitrate is bioactivated to nitrite and nitric oxide (NO) and has been used to treat cardiovascular and metabolic diseases. Patients with obesity or overweight are exposed to increased cardiovascular risk, which is in part attributable to increased matrix metalloproteinase (MMP) activity and cardiovascular remodeling. Here, we examined the effects of NO supplementation with oral nitrate treatment on the circulating concentrations of MMP-2, MMP-9, and their endogenous inhibitors, the tissue inhibitors of MMPs (TIMP-1,-2,-3 and -4) in overweight women who had previously undergone Roux-en-Y gastric bypass (RYGB) surgery (n = 15), and those with no history of bariatric procedures (control, n = 13). Patients received 5g of beetroot extract enriched with sodium nitrate to daily intake of 0.1 mmol/kg body weight of nitrate for 14 days. Ambulatory blood pressure monitoring, carotid-femoral pulse wave velocity (PWV), and the Augmentation Index (AIx) were assessed at baseline and after nitrate treatment. Venous blood samples were collected for biochemical analysis at baseline and after nitrate treatment. MMP-2, MMP-9, and TIMP-1,-2,-3 and -4 were assessed using two Human Luminex® Discovery Assays. Nitrite and nitrate concentrations were assessed using ozone-based reductive chemiluminescence methods. Nitrate treatment decreased net MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios (which reflect net MMP activity) in overweight control women, but not in those with previous bariatric surgery (All P < 0.05). Nitrite and nitrate concentrations were negatively associated with net MMP-2 and MMP-9 activity. While VOP showed no significant differences, MMP-2 concentrations or MMP-2/TIMP-2 ratio associated positively with AIx. Our results provide evidence that nitrate treatment reduces net MMP-2 and MMP-9 activity in overweight women, highlighting its therapeutic potential to prevent cardiovascular remodeling. However, this effect appears to be attenuated in women with prior RYGB surgery.