Plasma levels of matrix metalloproteinase-9: A possible marker for cold-induced stroke risk in hypertensive rats.

The cold weather is associated with an increased occurrence of acute stroke events. However, the underlying mechanisms have not yet been fully elucidated. In the present study, we investigated whether plasma matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels as well as the MMP-9/TIMP-1 ratio could be used as predictor for cold-induced stroke risk in hypertensive rats. A total of 50 male rats were subjected to either control group or 2-kidney, 2-clip (2K - 2C) group (N = 25, each), After blood pressure was stabilized, rats were placed in an intelligent artificial climate chamber and maintained on a 12-h light (22 °C)/dark (4 °C) cycle for 3 days. Plasma levels of MMP-9 and TIMP-1 were measured before and after cold exposure from 50 rats by ELISA. Pretreatment plasma MMP-9 levels were significantly higher in 2K-2C rats than in the controls (P <  0.05), TIMP-1 levels were significantly lower in 2K-2C rats than in the controls (P <  0.05), pretreatment plasma MMP-9 levels were significantly higher in those with cold-induced stroke compared to those without (P <  0.05). Logistic regression analysis showed that only plasma MMP-9 levels remained independently associated with cold-induced stroke after adjusting for potential confounders (OR, 1.17; 95% CI, 1.08 to 1.32; P < 0.007). In contrast, no correlation was observed between systolic blood pressure (SBP), TIMP-1 or MMP-9/TIMP-1 ratio and the cold-induced stroke. Higher plasma MMP-9 levels are significantly correlated with cold-induced stroke in hypertensive rats treated with intermittent cold stress. Plasma MMP-9 may be as a promising biomarker to predict the risk of cold-induced stroke events in hypertensive rats.