Sex-related differences in hypertrophy response and cardiac expression of G protein-coupled estrogen receptor in rats with pressure overload

• Published in: Gene Vol. 928; p. 148769
• Main Authors: Salehiyeh, Sajad, Alborzi, Nasrin, Azizian, Hossein, Esmailidehaj, Mansour, Hafizi Barjin, Zeinab, Safari, Fatemeh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.11.2024
• Subjects: Estrogen; Gender; Hypertrophy; Left Ventricular; Receptor; HDAC5; AAB; eNOS; Estrogen; RAAS; AKT; Gender; HW/BW; HFpEF; Left Ventricular; I/R; ER; BP; OVX; ERK1/2; CaMKII; PI3K; Receptor; GPER; CVDs; Hypertrophy; LVH
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2024.148769

[Display omitted] •Female and male rats are similar in baseline hemodynamic parameters and myocardial GPER expression.•Male rat hearts are more vulnerable to hypertrophy induced by pressure overload.•Female rat hearts exhibit higher myocardial GPER mRNA and protein expression levels in response to pressure overload.•Greater myocardial GPER expression in female rats during pressure overload may be responsible for stronger cardioprotection in this sex. There is increasing evidence that gender impacts the onset and progression of cardiovascular pathology. However, it is vastly unclear how this variable determines the ultimate outcomes, particularly in the setting of pressure overload-induced left ventricular hypertrophy (LVH). This study was carried out to fill this gap, at least in part, by assessing myocardial expression of G protein-coupled estrogen receptor (GPER) in female and male rats afflicted with LVH. Both female and male rats underwent abdominal aorta banding to induce LVH or were kept intact as control groups. At the end of the experiment, carotid artery catheterization was performed to measure systolic (SBP) and diastolic (DBP) blood pressure. Fibrosis and cardiomyocyte cross-sectional area were assessed by conventional histological analyses. Protein and mRNA expression were evaluated by Western blot/immunofluorescence staining and real-time RT-PCR technique, respectively. In LVH groups, male rats exhibited higher SBP and DBP, heart weight to body weight ratio, and fibrosis compared with female rats. However, both sexes showed a similar increase in cardiomyocyte size after LVH induction. In female, but not in male rats, LVH instigated the GPER mRNA and protein expression in the heart. These results, confirm a significant interaction between gender and myocardial remodeling in terms of GPER expression. Thus, it can be argued that sex differences in the cardiac GPER expression may be responsible for sex differences in the pressure overload-induced LVH. In other words, the female heart seems to unleash stronger protection against pressure overload than that of males in light of a higher GPER expression.