Key result
In utero exposure to hypoxia and indomethacin in rats induced pulmonary vascular remodeling, leading to cardiac hypertrophy, elevated cardiolipin and phosphatidylethanolamine, and mitochondrial dysfunction.
Why the study?
Pulmonary vascular remodeling in utero causes heart failure, but the alterations occurring in cardiac lipid and mitochondrial bioenergetics during its development were unknown.
In utero pulmonary vascular remodeling in a perinatal rat model leads to cardiac dysfunction that is associated with altered cardiolipin metabolism and mitochondrial bioenergetic defects.
Pulmonary vascular remodeling (PVR) in utero results in the development of heart failure. The alterations that occur in cardiac lipid and mitochondrial bioenergetics during the development of in utero PVR was unknown. In this study, PVR was induced in pups in utero by exposure of pregnant dams to indomethacin and hypoxia and cardiac lipids, echocardiographic function and cardiomyocyte mitochondrial function were subsequently examined. 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 a mitochondrial dysfunction. Although abundance of mitochondrial respiratory chain complexes was unaltered, increased trilinoleoyl-lysocardiolipin levels in these pups was observed. A compensatory increase in both cardiolipin and phosphatidylethanolamine content were observed due to increased synthesis of these phospholipids. These data indicate that 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.
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Cole et al. (2022) studied Pulmonary vascular remodeling (n=132). Hypoxia and indomethacin vs. Normoxia and PBS was evaluated on Cardiac cardiolipin and phosphatidylethanolamine levels, and mitochondrial bioenergetics (p=<0.05). In utero exposure to hypoxia and indomethacin in rats induced pulmonary vascular remodeling, leading to cardiac hypertrophy, elevated cardiolipin and phosphatidylethanolamine, and mitochondrial dysfunction.
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