Early-life exposure to lead changes cardiac development and compromises long-term cardiac function

Area of Science:

• Environmental Health
• Cardiovascular Biology
• Developmental Toxicology

Background:

• Lead (Pb) is a ubiquitous environmental toxicant with known adverse health effects.
• Early-life exposure to lead is a concern, but its impact on fetal heart development and long-term cardiac health remains unclear.

Purpose of the Study:

• To investigate the effects of early-life lead exposure on fetal heart development.
• To assess the long-term cardiac outcomes and susceptibility to secondary insults in adulthood.

Main Methods:

• Pregnant mice exposed to lead acetate trihydrate from gestation day 1.5 until offspring weaning.
• Offspring underwent a 'second hit' model with Angiotensin II infusion at 4 weeks old.
• Cardiac function assessed via echocardiography, histology, ultrastructural examination, and mitochondrial function tests.

Main Results:

• Early lead exposure caused cardiac abnormalities including reduced ejection fraction, increased ventricular volume, cardiomyocyte dysplasia, and mitochondrial dysfunction.
• Lead-exposed offspring showed heightened susceptibility to Angiotensin II-induced cardiac hypertrophy, fibrosis, apoptosis, and heart failure.
• Decreased expression of key sarcomeric and mitochondrial genes was observed in lead-exposed hearts.

Conclusions:

• Early-life low-dose lead exposure significantly compromises cardiac development and function.
• Lead exposure exacerbates cardiac pathological responses to secondary insults in adulthood.
• Provides evidence for lead's cardiac toxicity and informs risk evaluation for early-life exposure.