Perinatal Nicotine Exposure-Induced Cardiac Phenotype Is Mediated by miR-1-MIAT Interaction and Is Transmitted...

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Molecular Biology

Background:

• Perinatal nicotine exposure is linked to cardiac fibrosis, but mechanisms are unknown.
• Transgenerational inheritance of nicotine-induced phenotypes, like asthma, is documented.
• MicroRNA-1 (miR-1) and long noncoding RNA MIAT are implicated in cardiac injury.

Purpose of the Study:

• To investigate the transgenerational effects of perinatal nicotine exposure on the MIAT/miR-1/CTGF axis in rat hearts.
• To elucidate the molecular mechanisms underlying nicotine-induced cardiac fibrosis.

Main Methods:

• Perinatal nicotine exposure in Sprague-Dawley rats across F0, F1, and F3 generations.
• Quantitative real-time PCR and immunoblotting to assess MIAT, miR-1, and CTGF expression.
• Luciferase reporter assays and RNA immunoprecipitation to confirm MIAT sponging of miR-1.

Main Results:

• Perinatal nicotine exposure upregulated CTGF and MIAT, while downregulating miR-1 in F1 and F3 hearts.
• MIAT acts as a sponge for miR-1, and miR-1/MIAT modulation affects CTGF levels in cardiac fibroblasts.
• Nicotine exposure in vitro increased MIAT and CTGF, suppressing miR-1.

Conclusions:

• Perinatal nicotine exposure induces cardiac fibrosis via the MIAT/miR-1/CTGF axis.
• The cardiac phenotype and associated molecular alterations are transmitted transgenerationally.
• This study provides a novel mechanism for cardiac extracellular matrix deposition following perinatal nicotine exposure.