Table 1.
Reported evidence of oxidative stress and dysregulation of NOX enzymes in patients and animal models with HFpEF.
| Patients with HFpEF | Effect |
|---|---|
| Myocardium | • Trend towards increased NOX2 expression in cardiac macrophages [17] • Increased myocardial H2O2 levels [17,25] • Increased myocardial lipid peroxidation [25] |
| Serum | • Elevated levels of derivatives of reactive oxidative metabolites (DROMs) in patients with HFpEF with HF-related events [27,28] • Increased thiobarbituric acid reactive substances (TBARS, biomarker of lipid peroxidation) [19] |
| Peripheral Blood Monocytes | • Increased NOX1 and NOX4 mRNA levels correlate with diastolic dysfunction in patients with HFpEF [29] |
| Pre-clinical HFpEF Models | Effect |
| HFD †/L-NAME (mice) | • Increased myocardial Nox4 protein expression [30] |
| Unilateral nephrectomy and aldosterone infusion (mice) |
• Increased myocardial oxidative stress (DHE fluorescence) [23,24] |
| Obese ZSF1/ZDF rats | • Increased cardiac macrophage Nox2 [17] • Increased myocardial H2O2 levels [17,25] • Increased myocardial lipid peroxidation [25] |
| DOCA/Western diet †† (Göttingen miniswine) |
• Increased 8-isoprostane levels in plasma [20] |
| Streptozotocin, HFD †††, and renal artery embolization (Yorkshire x Landrace swine) |
• Increased myocardial NADPH-stimulated superoxide production [26] |
DHE, dihydroethidium (ROS sensor); DOCA, 11-deoxycorticosterone acetate (mineralocorticoid/glucocorticoid); DROMs, derivatives of reactive oxidative metabolites; HFD, high-fat diet; HFpEF, heart failure with preserved ejection fraction; L-NAME, Nω-nitro-L-arginine (NOS inhibitor); NADPH, nicotinamide adenine dinucleotide phosphate; TBARS, thiobarbituric acid reactive substances. Diet information: † 60% of calories from lard; †† 1% cholesterol, 20% fat, 8.9% fructose, 2% salt; ††† 10% sucrose, 15% fructose, 25% saturated fats, 1% cholesterol.