Anti-oxidative and anti-inflammatory role of adipose stem cells in reversing pulmonary hypertension and associated cardiac remodeling (1090.9)

Pulmonary Hypertension (PH) is a debilitating cardiopulmonary disorder, often resulting in right heart failure. Existing therapy does not curtail the rate of mortality. Here, the protective role of adipose stem cell (ADSC) in attenuating PH was studied. Monocrotaline (MCT) was injected into 8-weeks old male SD rats to induce PH. Post 2 weeks of MCT challenge, when the RVSP (Right Ventricular Systolic Pressure) was significantly elevated, ADSC were administered. After 4 weeks of MCT induction, RVSP (30.09±1.51 vs 86.71±4.21 mmHg), & RV Hypertrophy (RVH; 0.23±0.01 vs 0.60±0.03) were elevated. ADSC therapy significantly reduced RVSP (55.94±7.35) and RVH (0.34±0.04). Video of echocardiography demonstrated that RV end-diastolic area, (0.12±0.01 vs 0.33±0.03 cm2) and RV ejection fraction (61.62±0.93 vs 29.47±3.76 %) was significantly dysregulated in PH. Further, the pulmonary blood flow (0.88±0.04 vs 0.58±0.06 m/s) and AT/ET (0.37±0.01 vs 0.18±0.02) was altered by MCT treatment. ADSC reverted all of these cardiac remodeling events. RT-PCR demonstrated that the markers of fibrosis (TGFβ), pro-inflammatory cytokines (TLR4, TNFα, IL1β) and oxidative stress (NOX2) were up regulated 4 to 5 fold and anti-inflammatory cytokine (IL10) was down regulated 6 fold in PH animals. ADSC therapy normalized all of these parameters. Collectively, our data demonstrate that the anti-oxidant and anti-inflammatory role of ADSC arrested PH and associated cardiac remodeling and suggest that ADSC intervention could be a potential therapeutic alternative for the treatment of PH.