Differential cardiac geometry during pregnancy in lean versus obese mice.

BACKGROUND: Pregnancy is a sensitive window where factors adversely affecting maternal cardiac health may leave women vulnerable to cardiovascular disease (CVD) later in life. However, it is not clear how cardiac changes during pregnancy influence long-term cardiovascular health. Obesity, an independent risk factor for CVD, promotes adverse cardiac remodeling. Effects of obesity-mediated cardiac remodeling concurrent with physiologic cardiac hypertrophy of pregnancy are not well-studied. METHODS: Female C57BL/6J mice (8 weeks old) were fed a high fat (HF; 60% kcal from fat) or a control low fat (LF; 10% kcal from fat) diet for 8 weeks, then were crossed with male mice to become pregnant (P) or remained non-pregnant (NP) controls. After 18 days, cardiac morphology and function was quantified by echocardiography in LF and HF P and NP mice. RESULTS: Lean mice had increased left ventricular (LV) mass and LV end-diastolic diameter with pregnancy. In contrast, although LV mass was greater with obesity, it was not augmented with pregnancy in obese mice. Further, pregnant obese mice had decreased LV chamber diameter and increased relative wall thickness compared to lean mice. CONCLUSIONS: We report a differential cardiac geometry during pregnancy in lean versus obese mice in a mouse model of diet-induced obesity. These data suggest obesity during pregnancy promotes concentric remodeling, versus eccentric remodeling in lean mice. Adverse effects of obesity on cardiac remodeling during pregnancy may be an important contributor to subsequent maternal cardiovascular risk.

Cardiac hypertrophy with obesity is augmented after pregnancy in C57BL/6 mice.

BACKGROUND: Over a third of reproductive-age women in the USA are obese, and the prevalence of cardiovascular disease (CVD) is rising in premenopausal women. Cardiac hypertrophy is an independent predictor of CVD. In contrast to pregnancy, where transiently increased left ventricular (LV) mass is not associated with cardiac damage, obesity-mediated cardiac hypertrophy is pathological. There is a paucity of data describing the effect of obesity during pregnancy on maternal cardiovascular health. The purpose of this study was to determine the long-term effect of obesity during pregnancy on cardiac function and structure in mice. METHODS: Female C57BL/6 J mice were fed a high-fat (HF) or a low-fat (LF) diet for 20 weeks. After 4 weeks, LF- and HF-fed female mice were either crossed with males to become pregnant or remained non-pregnant controls. Following delivery, pups were euthanized, and females maintained on respective diets. After 20 weeks of diet feeding, cardiac function was quantified by echocardiography, and plasma leptin and adiponectin concentrations quantified in LF- and HF-fed postpartum and nulliparous females. mRNA abundance of genes regulating cardiac hypertrophy and remodeling was quantified from left ventricles using the NanoString nCounter Analysis System. Cardiac fibrosis was assessed from picrosirius red staining of left ventricles. RESULTS: HF-fed postpartum mice had markedly greater weight gain and fat mass expansion with obesity, associated with significantly increased LV mass, cardiac output, and stroke volume compared with HF-fed nulliparous mice. Plasma leptin, but not adiponectin, concentrations were correlated with LV mass in HF-fed females. HF feeding increased LV posterior wall thickness; however, LV chamber diameter was only increased in HF-fed postpartum females. Despite the marked increase in LV mass in HF-fed postpartum mice, mRNA abundance of genes regulating fibrosis and interstitial collagen content was similar between HF-fed nulliparous and postpartum mice. In contrast, only HF-fed postpartum mice exhibited altered expression of genes regulating the extracellular matrix. CONCLUSIONS: These results suggest that the combined effects of pregnancy and obesity augment cardiac hypertrophy and promote remodeling. The rising prevalence of CVD in premenopausal women may be attributed to an increased prevalence of women entering pregnancy with an overweight or obese BMI.