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Combined Statin and Glucocorticoid Therapy for the Safer Treatment of Preterm Birth
Andrew D Kane1, Emilio A Herrera1,2, Youguo Niu1,3,4
1Department of Physiology, Development and Neuroscience, University of Cambridge, United Kingdom (A.D.K., E.A.H., Y.N., E.J.C., B.J.A., C.L., K.L.B., C.M.C., D.A.G.).
Insights
Neonatal glucocorticoid treatment harms cardiovascular health by reducing nitric oxide (NO) bioavailability. Combined glucocorticoid and statin therapy protects infant cardiovascular systems by normalizing NO signaling, offering a safer treatment for preterm birth.
Area of Science:
- Neonatal medicine
- Cardiovascular research
- Pharmacology
Background:
- Prematurity is linked to poor neonatal respiratory function, often treated with glucocorticoids.
- Glucocorticoid therapy can cause long-term cardiovascular issues like hypertension and endothelial dysfunction.
- Glucocorticoid excess may harm the cardiovascular system by depleting nitric oxide (NO) bioavailability.
Purpose of the Study:
- To investigate the protective effects of combined glucocorticoid and statin therapy on the cardiovascular system in a rodent model of prematurity.
- To elucidate the molecular mechanisms underlying glucocorticoid-induced cardiovascular dysfunction and the potential benefits of statin co-administration.
Main Methods:
- Utilized a rodent model of prematurity.
- Conducted in vivo and ex vivo experiments assessing cardiovascular function.
- Performed cellular and molecular analyses to examine signaling pathways.
Main Results:
- Neonatal glucocorticoid treatment led to later cardiovascular dysfunction in offspring.
- Mechanisms included reduced NO bioavailability, sympathetic hyper-reactivity, and endothelial dysfunction.
- Combined therapy normalized NO and sympathetic signaling, preserving cardiovascular health without compromising lung benefits.
Conclusions:
- Combined glucocorticoid and statin therapy may mitigate cardiovascular risks associated with neonatal glucocorticoid treatment.
- This combined approach appears safer than glucocorticoids alone for managing preterm infants.
- The findings suggest a novel therapeutic strategy to protect the developing cardiovascular system in preterm neonates.
Background:
Prematurity is strongly associated with poor respiratory function in the neonate. Rescue therapies include treatment with glucocorticoids due to their anti-inflammatory and maturational effects on the developing lung. However, glucocorticoid treatment in the infant can increase the risk of long-term cardiovascular complications including hypertension, cardiac, and endothelial dysfunction. Accumulating evidence implicates a molecular link between glucocorticoid excess and depletion of nitric oxide (NO) bioavailability as a mechanism underlying the detrimental effects of postnatal steroids on the heart and circulation. Therefore, combined glucocorticoid and statin therapy, by increasing NO bioavailability, may protect the developing cardiovascular system while maintaining beneficial effects on the lung.
Methods:
We investigated combined glucocorticoid and statin therapy using an established rodent model of prematurity and combined experiments of cardiovascular function in vivo, with those in isolated organs as well as measurements at the cellular and molecular levels.
Results:
We show that neonatal glucocorticoid treatment increases the risk of later cardiovascular dysfunction in the offspring. Underlying mechanisms include decreased circulating NO bioavailability, sympathetic hyper-reactivity, and NO-dependent endothelial dysfunction. Combined neonatal glucocorticoid and statin therapy protects the developing cardiovascular system by normalizing NO and sympathetic signaling, without affecting pulmonary maturational or anti-inflammatory effects of glucocorticoids.
Conclusions:
Therefore, combined glucocorticoid and statin therapy may be safer than glucocorticoids alone for the treatment of preterm birth.
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