Abstract Body: Background: Neonatal anemia stresses the developing heart, leading to early hypertrophy. Detecting changes in preterm infants is difficult due to rapid cardiac maturation and imaging limitations. Fluid and metabolic regulation is crucial for the stressed heart. The role of Aquaporins in the neonatal heart during anemia is under-researched. We explored whether changes in Aquaporin expression indicate an early response to anemia-induced stress.
Hypothesis: Aquaporin (AQP)-8 mediates cardiac remodeling in anemic neonates by linking mitochondrial stress to metabolic disturbances.
Objective: To determine the tissue source, temporal pattern, and functional significance of AQP8 upregulation in anemia-induced cardiac stress in neonatal mice.
Methods: C57BL/6 pups (n=6), both sexes, were assigned to naïve controls or severely anemic groups (phlebotomy on days 2, 4, 6, 8, and 10; hematocrit 20-24%). Cardiac remodeling was assessed via histopathology, heart rate, and arterial oxygen saturation. Metabolic status and acid-base parameters were measured with an ABG analyzer, while aquaporin expression in cardiac tissue was analyzed through qPCR, immunoblotting, and immunohistochemistry.
Results: At P11, anemic neonates exhibited enlarged cardiomyocytes, increased heart rates (605.7 vs. 546.7 bpm), and low oxygen saturation (41.9% vs. 95.5%), indicating cardiovascular stress. Metabolic results included acidosis (pH 7.01 vs 7.39), elevated pCO2 (38.2 vs. 23.3 mmHg), low bicarbonate (9.8 vs. 14.2 mEq/L), decreased hematocrit (27% vs. 42%), and hyperglycemia (142 vs. 83 mg/dL). AQP8 was upregulated (4.44-fold vs. control) starting on day 6. Notably, circulating AQP8 in blood (9.96 ± 0.23-fold vs control) increased in parallel with the cardiac rise. AQP8 is a mitochondrial protein; we measured MT-ND1 across tissues. MT-ND1 was significantly higher in the heart on day 6 compared to liver and intestine, indicating cardiac mitochondrial stress as the primary source. Immunohistochemistry with TOM20 showed increased AQP8 expression in anemic hearts, highlighting AQP8's role in cardiac stress adaptation linked to anemia-related metabolic acidosis and mitochondrial stress.
Conclusions: AQP8 is identified as a novel mediator of anemia-induced cardiac stress in neonatal mice, with elevated levels indicating its potential as an early marker of subclinical remodeling.