Impact of serum uric acid on subclinical myocardial injury in general population.

BACKGROUND AND AIMS: Hyperuricemia is widely thought as a risk factor for myocardial infarction (MI) and all-cause mortality; however, the relation of serum uric acid (sUA) and subclinical myocardial injury (SCeMI) remains unclear. We hypothesize that sUA is associated with subclinical myocardial injury. METHODS AND RESULTS: A total of 5880 adult individuals (57.9 ± 13.0 years, 54.23% women) without known cardiovascular disease from National Health and Nutrition Examination Survey (NHANES) III were included. Determined by Cardiac Infarction Injury Score (CIIS) from 12-lead electrocardiogram, SCeMI was defined by CIIS ≥10 units. The relationship between sUA and SCeMI was analyzed by using logistic regression models and the smooth curve fitting. Subgroup analyses were conducted. After adjusting for potential confounding variables, the smooth curve fitting revealed a non-linear relationship between sUA level and SCeMI. When sUA was above the inflection point 266.5 µmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 15%. In women group, when sUA>340.3 µmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 71%, but no significant correlation was observed in men group. CONCLUSIONS: Our findings confirm that sUA is an independent risk factor for subclinical myocardial injury after adjusting for potential confounding variables, and existence of such an association in women only, which require more random control trials to confirm the strategy of cardiovascular disease prevention based on sUA reduction in female.

High uric acid promotes mitophagy through the ROS/CaMKIIδ/Parkin pathway in cardiomyocytes in vitro and in vivo.

BACKGROUND: Increasing evidence has suggested that high uric acid (HUA) is closely related to cardiovascular disease (CVD). Mitophagy abnormalities have been reported to participate in multiple pathogenic processes of CVD. However, the potential molecular mechanisms remain unclear. Herein, we investigated the effect of HUA-induced mitophagy and its potential molecular mechanism in cardiomyocytes. METHODS: We established a model of cardiomyocytes induced by HUA in vitro and in vivo. Mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production and adenosine triphosphate (ATP) content were measured. The mitophagy-related protein expression of LC3B-II, Parkin, Ca2+/calmodulin-dependent protein kinase II δ (CaMKIIδ) and P62 was measured by Western blot. Based on the colocalization of lysosomes and mitochondria, a confocal microscope was used to detect mitophagy. Additionally, we established a mitophagy inhibitor group (3-MA) and CaMKIIδ inhibitor group (KN-93) to verify the pathway. RESULTS: In the HUA stimulation model, ROS production was increased, and mitochondrial injury indexes (MMP and ATP contents) were decreased. Moreover, these indicators were reversed by 3-MA and KN-93. Under HUA stimulation, the expression of LC3B-II, Parkin, CaMKIIδ and P62 increased significantly. Furthermore, these protein levels were reduced by 3-MA and KN-93. CONCLUSION: HUA can promote cardiomyocyte mitophagy activation through the ROS/CaMKIIδ/parkin pathway axis. This study may provide a new target and theoretical basis for the prevention and treatment of HUA-related metabolic heart disease in the future.