Prenatal exposure to lipopolysaccharide results in myocardial remodelling in adult murine offspring.
BACKGROUND
The epigenetic plasticity hypothesis indicates that pregnancy exposure may result in adult-onset diseases, including hypertension, diabetes and cardiovascular disease, in offspring. In a previous study, we discovered that prenatal exposure to inflammatory stimulants, such as lipopolysaccharides (LPS), could lead to hypertension in adult rat offspring. In the present study, we further demonstrate that maternal inflammation induces cardiac hypertrophy and dysfunction via ectopic over-expression of nuclear transcription factor κB (NF- κB), and pyrrolidine dithiocarbamate (PDTC) can protect cardiac function by reducing maternal inflammation.


METHODS
Pregnant SD rats were randomly divided into three groups and intraperitoneally injected with a vehicle, LPS (0.79 mg/kg), or LPS (0.79 mg/kg) plus PDTC (100 mg/kg) at 8 to 12 days of gestation. The offspring were raised until 4 and 8 months old, at which point an echocardiographic study was performed. The left ventricular (LV) mass index and apoptosis were examined.


RESULTS
At 4 months of age, the LPS offspring exhibited augmented posterior wall thickness. These rats displayed left ventricle (LV) hypertrophy and LV diastolic dysfunction as well as a higher apoptotic index, a higher level of Bax and a lower level of Bcl-2 at 8 months of age. The protein levels of NF-κB (p65) in the myocardium of the offspring were measured at this time. NF-κB protein levels were higher in the myocardium of LPS offspring. The offspring that were prenatally treated with PDTC displayed improved signs of blood pressure (BP) and LV hypertrophy.


CONCLUSIONS
Maternal inflammation can induce cardiac hypertrophy in offspring during aging accompanied with hypertension emergence and can be rescued by the maternal administration of PDTC (the inhibitor of NF-κB).
The Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, The Third Military Medical University, Chongqing, China ; Department of Gastroenterology, Research Institute of Surgery, Da ping Hospital, The Third Military Medical University, Chongqing, China.
Yanling
Y
Wei
Department of Ultrasound, Research Institute of Surgery, Da ping Hospital, The Third Military Medical University, Chongqing, China.
Wenhua
W
Du
Department of Ultrasound, Research Institute of Surgery, Da ping Hospital, The Third Military Medical University, Chongqing, China.
Xiuqin
X
Xiong
The Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, The Third Military Medical University, Chongqing, China.
Xiaoyan
X
He
Department of Gynaecology, Research Institute of Surgery, Da ping Hospital, The Third Military Medical University, Chongqing, China.
Ping Yi
The Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, The Third Military Medical University, Chongqing, China.
Youcai
Y
Deng
Department of Gastroenterology, Research Institute of Surgery, Da ping Hospital, The Third Military Medical University, Chongqing, China.
Dongfeng
D
Chen
The Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, The Third Military Medical University, Chongqing, China.
Xiaohui
X
Li
Foetal development; Inhibitor of NF-κB; Maternal inflammation; Myocardial remodelling