Key result
In utero exposure to hypoxia and indomethacin induced pulmonary vascular remodeling in perinatal rat pups, resulting in cardiac hypertrophy, ventricular dysfunction, and mitochondrial dysfunction associated with elevated cardiolipin and phosphatidylethanolamine levels.
Why the study?
Pulmonary vascular remodeling in utero causes heart failure, but the alterations in cardiac lipid and mitochondrial bioenergetics during its development were unknown.
In a perinatal rat model of pulmonary vascular remodeling, altered cardiac cardiolipin and phospholipid metabolism is associated with mitochondrial bioenergetic and cardiac functional defects.
Background Pulmonary vascular remodeling (PVR) in utero results in the development of heart failure (HF). The alterations that occur in cardiac lipid and mitochondrial bioenergetics during the development of in utero PVR was unknown. Methods PVR was induced in pups in utero by exposure of pregnant dams to indomethacin and hypoxia. Cardiac lipids, echocardiographic function and cardiomyocyte mitochondrial function were subsequently examined. Results Perinatal rat pups with PVR exhibited elevated left and right cardiac ventricular internal dimensions and reduced ejection fraction and fractional shortening compared to controls. Cardiac myocytes from these pups exhibited increased glycolytic capacity and glycolytic reserve compared to controls. However, respiration with glucose as substrate was unaltered. Fatty acid oxidation and ATP-insensitive respiration were increased in isolated cardiac myocytes from these pups compared to controls indicating mitochondrial dysfunction. Although abundance of mitochondrial respiratory complexes were unaltered, increased trilinoleoyl-lysocardiolipin levels in these pups was observed. A compensatory increase in both cardiolipin (CL) and phosphatidylethanolamine (PE) content were observed due to increased synthesis of these phospholipids. Conclusion Alterations in cardiac cardiolipin and phospholipid metabolism in PVR rat pups is associated with the mitochondrial bioenergetic and cardiac functional defects observed in their hearts. Impact statement - Phospholipid metabolism was examined in pulmonary vascular remodeling in perinatal rat pups. - Pulmonary vascular remodeling was induced in utero by treating pregnant dams with hypoxia and indomethacin at 19-21 days of gestation. - The offspring exhibited altered pulmonary arterial remodeling with subsequent cardiac hypertrophy, ventricular dysfunction, cardiac myocyte mitochondrial dysfunction with altered fatty acid utilization. - In addition, the offspring exhibited elevated cardiolipin, lysocardiolipin and phosphatidylethanolamine content which may potentially contribute to the cardiac mitochondrial dysfunction.
No takes yet. Share an insight, caveat, or question.
Cole et al. (2021) studied Pulmonary vascular remodeling. Hypoxia and indomethacin vs. Control (PBS and normoxia) was evaluated on Cardiac morphology, mitochondrial function, and phospholipid composition. In utero exposure to hypoxia and indomethacin induced pulmonary vascular remodeling in perinatal rat pups, resulting in cardiac hypertrophy, ventricular dysfunction, and mitochondrial dysfunction associated with elevated cardiolipin and phosphatidylethanolamine levels.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: