We aimed to study the effects of long-term statin administration to high fat (HF)-fed female mice from the time they were weaned through to pregnancy and lactation on cardiovascular and metabolic risk factors in their HF-fed offspring. Female C57 mice on HF (45% kcal fat) were given pravastatin in their drinking water from the time they were weaned, during pregnancy and lactation. Weaned offspring were then fed an HF diet until adulthood generating the dam/offspring dietary groups HF/HF and HF plus pravastatin from the time dams were weaned, during pregnancy and lactation/HF (HF+S/HF). These groups were compared with offspring from mothers fed standard chow (control) which were then fed a control diet up to adulthood (control/control; C/C). HF+S dams showed significantly reduced total cholesterol concentrations and systolic blood pressure (SBP) versus HF dams. The reduction in total cholesterol and SBP in the HF+S dams did not restore values to those observed in the C group. Both male and female HF+S/HF offspring were significantly lighter in weight, and had lower SBP and serum cholesterol concentrations versus HF/HF. HF/HF offspring had elevated C-reactive protein levels but HF+S/HF animals of both sexes had reduced levels similar to those found in the C/C group. Long-term pravastatin administration to dams not only protects them from the deleterious effects of an HF diet, but this long-term maternal statin protection also has an equal and permanent effect in both male and female offspring up to their adult life, which is a novel finding.

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