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Sex‐specific cultures of neonatal cardiomyocytes possess differential cellular and biochemical properties in response to induced hypertrophy
Author(s) -
Ross Abigail,
Deaton Michael,
Waikel Rebekah
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1119.12
Subject(s) - muscle hypertrophy , endocrinology , medicine , atrial natriuretic peptide , phenylephrine , estrogen , biology , angiotensin ii , blood pressure
It is well established that premenopausal women develop cardiovascular disease (CVD) at a lower rate of incidence than men. However, it is not well understood how estrogen and other female‐specific factors prevent the development of CVD, including cardiac hypertrophy and heart failure. Using a sex‐specific primary neonatal rat cardiomyocyte culture system, we sought to define cellular sex‐specific responses to known hypertrophy agents phenylephrine (PE) and angiotensin‐II (AngII) in the presence or absence of estradiol (E2), a known anti‐hypertrophic agent. Postnatal, day‐2 rat pups were sexed based on the presence or absence of ovaries and uterus, and same‐sex hearts were combined for primary cardiomyocyte cultures accompanied by a fibroblast removal step. Sex‐specific cardiomyocyte cultures were established and treated with PE or AngII to induce hypertrophy in the presence or absence of E2, after which cell size and gene expression were assessed. Interestingly, untreated male and female primary cultures exhibited significant differences on the cellular level. Male cardiomyocytes possess a larger base line cell surface area as compared to female cardiomyocytes. Male cultures also proliferate more rapidly, as confirmed by cell counts and BrdU incorporation analysis. Both male and female cultures demonstrated similar increases in cell size in response to hypertrophy agents. Male cultures were found to be more responsive to the attenuating effects of E2. Hypertrophy markers including Brain Natriuretic Peptide (BNP), Atrial Natriuretic Peptide (ANP), MHC‐alpha, and MHC‐beta were also differentially expressed in a sex‐specific manner in response to PE and AngII. Gene expression analysis of proteins known to contribute to the hypertrophy phenotype, such as the Tumor Growth Factor Beta (Tgfβ) family, also demonstrated both estrogen and sex‐specific regulation. These observed variations in sex‐specific cardiomyocyte cultures may be a key to understanding male and female differences in CVD pathogenesis.