Abstract 1107: Systemic Interleukin-10 Expression Prevents Hypertension and Heart Failure through Upregulation of Heme Oxygenase-1 in Dahl Salt-sensitive Rats.
Introduction: Recent studies suggested that inflammation might be related to prehypertension. In this study, we investigated the effects of interleukin (IL)-10, a pleiotropic anti-inflammatory cytokine, on prehypertension and hypertensive heart disease to explore a potential application of anti-inflammatory therapy.
Methods: The male Dahl salt-sensitive rats were injected with the adeno-associated virus (AAV) vectors which express rat IL-10 or EGFP at 5 weeks old and were fed a high-sodium diet from 6 weeks old. Systolic blood pressure (sBP) and echocardiographic findings were periodically assessed. Serum IL-10 and TNF-α levels were measured using ELISA. Serum asymmetric dimethylarginine (ADMA) level was determined using HPLC. At 9 and 20 weeks old, endothelial nitric oxide synthase (eNOS) quantitative RT-PCR analysis, eNOS and heme oxygenase (HO)-1 protein measurement, and pathological studies were performed.
Results: Six weeks after injection of the vectors, serum IL-10 level significantly increased in the IL-10 group compared to the EGFP group (418 vs. 0 pg/ml, p<0.0001). Serum TNF-α level significantly decreased at 20 weeks old in the IL-10 group (0 vs. 7.1 pg/ml). At 9 weeks old, sBP of the IL-10 group significantly improved. This effect persisted over 2 months after transduction (175 ± 14 vs. 231 ± 9 mmHg, p<0.0001, at 18 weeks old). Furthermore, sBP negatively correlated with level of IL-10 at 13 weeks after transduction (r = -0.90, P<0.0001, n = 19). Both eNOS mRNA and protein levels in the aorta as well as the serum concentration of ADMA had no significant differences between IL-10 and EGFP group. Interestingly, HO-1 level in the kidney increased at 9 weeks old in the IL-10 group (26.6 ± 9.5 vs. 7.7 ± 1.2 pg/mg protein, p<0.05). sBP negatively correlated with HO-1 level (r = -0.81, P<0.05, n = 6). The LV hypertrophy, systolic LV dysfunction, and fibrotic change in the heart also ameliorated in the IL-10 group. Furthermore, survival rate at 20 weeks old significantly improved in the IL-10 group (100 vs. 0%).
Conclusion: Systemic IL-10 expression might suppress the progression of hypertension and heart failure through a novel HO-1 pathway. Anti-inflammatory therapy using IL-10 would be a promising strategy of prehypertension and hypertensive heart disease.