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Gender differences of gene expression profiles in brain cardiovascular centers of SHRs [hypothalamus]

ABSTRACT: Arterial pressure (AP) is lower in pre-menopausal women than in men of similar age. Pre-menopausal women exhibit a lower sympathetic outflow and a greater baroreceptor reflex, however molecular mechanisms for the gender differences of AP regulation are still not well understood. Since the hypothalmus is strongly functionnaly connected to the nucleus tractus solitarius (NTS), a pivotal region of the medulla oblongata for regulating the set-point of AP, we hypothesized that a different neuronal functions at the level of hypothalamus between men and women could contribute to the gender difference in cardiovascular homeostasis. Since females Spontaneous Hypertensive Rats (SHRs) clearly exhibit lower AP levels than their male counterparts at similar age, we investigated whether the hypothalamus of SHRs exhibit gender differences in gene expression by using microarray technique.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE100198 | GEO | 2018/01/30

SECONDARY ACCESSION(S): PRJNA390976

REPOSITORIES: GEO

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Project description:Historically, lower incidence of CVD and related deaths in women compared to men of the same age has been attributed to female sex hormones, particularly estrogen and its receptors. Autologous Bone marrow stem cell (BMSC) clinical trials for cardiac cell therapy overwhelmingly included male patients; however, meta-analysis data on these trials suggest a better functional outcome in women compared to men. Direct comparison of gender-specific cardiac reparative activity and estrogen-independent mechanisms that regulate gender-specific dimorphisms of BMSC has not been studied. This study was designed to identify sex hormone-independent mechanisms that regulate superior reparative properties of female endothelial progenitor cells (EPCs) post-MI, particularly epigenetic mechanisms. Male (M), female (F), and ovariectomized female (OVX) mice-derived EPCs were subjected to a series of molecular and epigenetic analyses followed by in vivo functional assessments of cardiac repair. RNA sequencing and other quantitative assays showed a similar genetic profile between F-EPCs and OVX-EPCs, distinct from M-EPCs that displayed significant up-regulation of inflammation-related genes. F-EPCs and OVX EPCs secrete higher levels of proangiogenic factors, lower levels of proinflammatory cytokines and show better cardiac reparative activity after intra-cardiac injections in a male mouse model of myocardial infarction (MI). Epigenetic sequencing revealed a marked difference in the occupancy of the gene repressive H3K9me3 mark, particularly at transcription start sites of key angiogenic and proinflammatory genes in male EPCs compared to female and ovariectomized EPCs. Our study unveiled that functional gender dimorphism in EPCs is, in part, mediated by differential epigenetic regulation of the proinflammatory and anti-angiogenic gene CCL3, orchestrated by the control of H3K9me3 by histone methyltransferase, G9a/Ehmt2. Our research highlights the importance of considering gender of donor cells for progenitor based tissue repair.

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Gender differences of gene expression profiles in brain cardiovascular centers of SHRs [hypothalamus]

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