PT  - JOURNAL ARTICLE
AU  - Sairam Thiagarajan
AU  - Amit N. Patel
AU  - Meenu Subrahmanian
AU  - Rajendran Gopalan
AU  - Steven M. Pogwizd
AU  - Sudha Ramalingam
AU  - Sankaran Ramalingam
AU  - Namakkal S. Rajasekaran
TI  - Evidence for a hyper-reductive redox in a sub-set of heart failure patients
AID  - 10.1101/246413
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 246413
4099  - http://biorxiv.org/content/early/2018/01/11/246413.short
4100  - http://biorxiv.org/content/early/2018/01/11/246413.full
AB  - Background Oxidative stress has been linked to heart failure (HF) in humans. Antioxidant-based treatments are often ineffective. Therefore, we hypothesize that some of the HF patients might have a reductive stress (RS) condition. Investigating RS-related mechanisms will aid in personalized optimization of redox homeostasis for better outcomes among HF patients.Methods Blood samples were collected from HF patients (n=54) and healthy controls (n=42) and serum was immediately preserved in –80°C for redox analysis. Malondialdehyde (MDA; lipid peroxidation) levels by HPLC, reduced glutathione (GSH) and its redox ratio (GSH/GSSG) using enzymatic-recycling assay in the serum of HF patients were measured. Further, the kinetics of key enzymatic-antioxidant enzymes was analyzed by UV-Vis spectrophotometry. Non-invasive echocardiography was used to relate circulating redox status with cardiac function and remodeling.Results The circulatory redox state (GSH/MDA ratio) was used to stratify the HF patients into normal redox (NR), hyper-oxidative (HO), and hyper-reductive (HR) groups. While the majority of the HF patients exhibited the HO (42%), 41% of them had a normal redox (NR) state. Surprisingly, a subset of HF patients (17%) belonged to the hyper-reductive group, suggesting a strong implication for RS in the progression of HF. In HF patients, SOD, GPx and catalase were significantly increased while GR activity was significantly reduced relative to healthy controls. Furthermore, echocardiography analyses revealed that 55% of HO patients had higher systolic dysfunction while 75% of the hyper-reductive patients had higher diastolic dysfunction.Conclusion These results suggest that RS may be associated with HF pathogenesis for a subset of cardiac patients. Thus, stratification of HF patients based on their circulating redox status may serve as a useful prognostic tool to guide clinicians designing personalized antioxidant therapies.