AI Article Synopsis

  • The study investigates the relationship between nitric oxide (NO) and endothelin-1 (ET-1) systems in the heart, highlighting how these systems contribute to diastolic dysfunction and exhibit sexual dimorphisms in mice.
  • It shows that male eNOS-/- mice have higher ET-1 expression and develop specific heart issues like cardiomyocyte hypertrophy and increased blood pressure, which are not observed in females.
  • The findings emphasize the importance of considering sex differences when studying cardiovascular disease mechanisms, potentially impacting treatment and understanding of these conditions in humans.

Article Abstract

Aims: The nitric oxide and endothelin systems are key components of a local paracrine hormone network in the heart. We previously reported that diastolic dysfunction observed in mice lacking the endothelial nitric oxide synthase (eNOS-/-) can be prevented by a genetic overexpression of ET-1. Sexual dimorphisms have been reported in both ET-1 and NO systems. Particularly, eNOS-/- mice present sex related phenotypic differences.

Main Methods: We used the ET-1 transgenic (ET+/+), eNOS-/-, and crossbred ET+/+eNOS-/- mice, and wild type controls. We measured cardiac function by heart catheterization. Cardiac ventricles were collected for histological and molecular profiling.

Key Findings: We report here that (i) the level of ET-1 expression in eNOS-/- mice was elevated in males but not in females. (ii) Left ventricular end-diastolic blood pressure was higher in male eNOS-/- mice than in females. (ii) eNOS-/- males but not females developed cardiomyocyte hypertrophy. (iv) Perivascular fibrosis of intracardiac arteries developed in female ET+/+ and eNOS-/- mice but not in males. Additionally, (v) the cardiac expression of metalloprotease-9 was higher in eNOS-/- males compared to females. Finally, (vi) cardiac proteome analysis revealed that the protein abundance of the oxidative stress related enzyme superoxide dismutase presented with sexual dimorphism in eNOS-/- and ET+/+ mice.

Significance: These results indicate that the cardiac phenotypes of ET-1 transgenic mice and eNOS knockout mice are sex specific. Since both systems are key players in the pathogenesis of cardiovascular diseases, our findings might be important in the context of gender differences in patients with such diseases.

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Source
http://dx.doi.org/10.1016/j.lfs.2013.12.003DOI Listing

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