Cardiovascular Impact of Prenatal Methamphetamine

Prenatal exposure to CNS stimulants such as cocaine, methamphetamine, caffeine, and nicotine can lead to physiological changes that persist into adulthood.  Most work describing the impact of fetal exposure to methamphetamine has focused on neurological outcomes.  Relatively little is known regarding the impact of prenatal exposure to methamphetamine on the adult cardiovascular system.  Our laboratory has found that prenatal exposure to methamphetamine increases susceptibility to cardiac ischemic injury during adulthood and alters the expression and phosphorylation status of proteins (protein kinase C-ε and Akt) that have well established roles in cardioprotection.  Importantly, we have observed these cardiac effect of prenatal methamphetamine exclusively in female hearts.  Their male littermates were unaffected. One goal of our laboratory is to understand the cardiovascular impact of prenatal methamphetamine exposure.

Our laboratory has reported that exposure to methamphetamine during early adulthood also causes sex-dependent changes in the heart.  Methamphetamine causes female hearts (but not male hearts) to become hypersensitive to ischemic injury.  RNA sequencing studies have demonstrated that female hearts are also much more sensitive than male hearts to methamphetamine-induced changes in gene expression (both in terms of the number of genes that are altered and the magnitude of the changes). 

Relevant Publications:

Chavva H, Brazeau DA, Denvir J, Primerano DA, Fan J, Seeley SL, Rorabaugh BR (2021) Methamphetamine-induced changes in myocardial gene transcription are sex-dependent. BMC Genomics. In press.

Rorabaugh BR (2021) Does prenatal exposure to CNS stimulants increase the risk of cardiovascular disease in adult offspring? Frontiers in Cardiovascular Medicine. 8:652634.

Seeley SL, D’Souza MS, Stoops TS, Rorabaugh BR (2020). Short term methylphenidate treatment does not increase myocardial injury in the ischemic rat heart. Physiological Research 69:803-812.

Rorabaugh BR, Seeley SL, Stoops TS, D’Souza MS (2017). Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart. PLOS ONE 12:e0179129.

Rorabaugh BR, Seeley SL, Bui AD, Sprague L, D’Souza MS. (2016) Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult rat hearts. American Journal of Physiology 310:H516-523.