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other·pediatrics, obstetrics and gynecology, cardiology, preclinical research, biomedical research·PMC10017302

Combined Statin and Glucocorticoid Therapy for the Safer Treatment of Preterm Birth

Hypertension (Dallas, Tex. : 1979) · 13 authors, 8 centres

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TL;DR

This preclinical study used a rodent model to test whether adding the statin pravastatin to dexamethasone therapy for prematurity could protect the cardiovascular system.

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The findings support the hypothesis that combined glucocorticoid and statin therapy may be a safer approach for treating preterm birth by protecting the developing cardiovascular system.

STUDY TYPE

other

SPECIALTY

pediatrics

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ORIGINAL PAPER

PMC10017302

Combined Statin and Glucocorticoid Therapy for the Safer Treatment of Preterm Birth

Hypertension (Dallas, Tex. : 1979)

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ABSTRACT

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.

CITATION EXPORT

Andrew D. Kane, Emilio A. Herrera, Youguo Niu et al.. Combined Statin and Glucocorticoid Therapy for the Safer Treatment of Preterm Birth. Hypertension (Dallas, Tex. : 1979). (2023). https://doi.org/10.1161/HYPERTENSIONAHA.122.19647

AUTHORS

13 · 8 CENTRES

Andrew D. Kane, Emilio A. Herrera, Youguo Niu, Emily J. Camm, Beth J. Allison, Deodata Tijsseling, Ciara Lusby, Jan B. Derks, Kirsty L. Brain, Inge M. Bronckers, Christine M. Cross, Lindsey Berends, Dino A. Giussani

Department 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.).
Laboratory of Vascular Function & Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile (E.A.H.).
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia (E.J.C., B.J.A.).
Perinatal Center, University Medical Center, Utrecht, the Netherlands (D.T., J.B.D.).
Institute of Metabolic Science, University of Cambridge Metabolic Research Laboratories, Addenbrooke’s Hospital, Cambridge, United Kingdom (L.B.).
Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, the Netherlands (I.M.B.).
The Cambridge BHF Centre for Research Excellence, Cambridge, United Kingdom (Y.N., D.A.G.).
The Cambridge Strategic Research Initiative in Reproduction, Cambridge, United Kingdom (Y.N., D.A.G.).