In utero chronic intermittent nicotine aerosol exposure increases ischemic heart injury in adult offspring via programming of Angiotensin II receptor-derived TGFβ/ROS/Akt signaling pathway.
Wansu YuZewen ChenYong LiSiyi JiangLubo ZhangXuesi M ShaoDaLiao XiaoPublished in: Reproductive toxicology (Elmsford, N.Y.) (2024)
Fetal nicotine aerosol exposure leads to cardiac dysfunction in response to ischemic stimulation in adulthood. Two molecular pathways are implicated. First, fetal CINA exposure elevates cardiac ATR levels, affecting the TGFβ-SMADs pathway. Second, heightened Angiotensin II/ATR signaling triggers ROS production, leading to DNA hypermethylation, p-Akt activation, and autophagy deficiency. These molecular shifts in cardiomyocytes result in the development of a heart ischemia-sensitive phenotype and subsequent dysfunction in adult offspring.
Keyphrases
- angiotensin ii
- signaling pathway
- angiotensin converting enzyme
- vascular smooth muscle cells
- transforming growth factor
- cell death
- oxidative stress
- epithelial mesenchymal transition
- dna damage
- pi k akt
- heart failure
- cell proliferation
- left ventricular
- high fat diet
- single molecule
- smoking cessation
- dna damage response
- ischemia reperfusion injury
- induced apoptosis
- depressive symptoms
- atrial fibrillation
- type diabetes
- childhood cancer
- adipose tissue
- circulating tumor
- cerebral ischemia
- replacement therapy
- subarachnoid hemorrhage