Since 2012, Virender K. Rehan, MD, an investigator at The Lundquist Institute for Biomedical Innovation, has studied how perinatal nicotine exposure affects health across generations. Building on earlier work from his laboratory showing that nicotine exposure can transmit asthma-related changes across generations, Dr. Rehan and his team sought to determine whether similar long-term effects might also extend to the heart.
In a recent study published in The FASEB Journal, Dr. Rehan and colleagues used a rat model to examine how nicotine exposure during pregnancy and early life affects cardiac health in offspring. They found increased cardiac fibrosis, or scar-like buildup in heart tissue, not only in directly exposed offspring but also in third-generation descendants that had no direct nicotine exposure.
To better understand how this may occur, the team investigated a molecular pathway involving MIAT, miR-1, and CTGF. Their findings showed increased MIAT and CTGF, along with reduced miR-1, in both directly exposed animals and later-generation offspring. These changes were associated with cardiac fibrosis and suggest a possible mechanism by which nicotine exposure may contribute to long-lasting and even transgenerational effects on the heart.
The findings raise important questions about how nicotine-related injury may be biologically transmitted across generations. Dr. Rehan is particularly interested in whether male and female germlines may contribute differently to these effects, as well as whether similar mechanisms may influence other organ systems.
“This is the first transgenerational study in this area to include a third generation,” said Dr. Rehan. “It opens the door to more focused investigation of cardiac risk, epigenetic mechanisms, and the possibility that nicotine exposure whether from combustible cigarettes, electronic cigarettes, or any other source may affect multiple organs across generations.”
Although these findings come from an animal model and further work is needed to determine how they apply to humans, they add to growing concern about the long-term biological consequences of nicotine exposure during critical developmental windows.
For communities with high rates of tobacco or nicotine-product use, this research may also carry broader public health relevance. “There is an opportunity to use these findings to strengthen awareness of the potential long-term and even multigenerational consequences of nicotine-based products,” Dr. Rehan said.
Read the full study in The FASEB Journal:
https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.202504804R