Transcriptomics and proteomics revealed sex differences in human pulmonary microvascular endothelial cells

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Biology
• Pulmonary Hypertension Research

Background:

• Pulmonary hypertension (PH) exhibits significant sexual dimorphism in onset, progression, and survival.
• Pulmonary microvascular endothelial cells are critical in PH pathogenesis, influencing vascular remodeling and resistance.
• Existing research suggests sex differences in PH, but the underlying endothelial mechanisms independent of sex hormones remain unclear.

Purpose of the Study:

• To investigate sex differences in human pulmonary microvascular endothelial cells (HPMECs) basally and under hypoxia, independent of sex hormones.
• To identify molecular pathways and cellular behaviors that differ between male and female HPMECs.
• To explore potential mechanisms contributing to the sexual dimorphism observed in pulmonary hypertension.

Main Methods:

• Human pulmonary microvascular endothelial cells (HPMECs) from healthy male and female donors were cultured under physiological shear stress.
• RNA sequencing and label-free quantitative proteomics were employed to analyze molecular differences.
• Gene set enrichment analysis was used to identify differentially regulated pathways.

Main Results:

• Significant sex-based differences in RNA and protein expression were identified in HPMECs under both normoxia and hypoxia.
• Pathways regulating cell proliferation showed sex-specific regulation.
• Female HPMECs exhibited a lower proliferation rate compared to male HPMECs, with higher thrombospondin-1 expression in female cells.

Conclusions:

• This study reveals intrinsic sex differences in HPMECs, persisting even without hormonal influence.
• Identified sex-different pathways provide novel insights into the sexual dimorphism of pulmonary hypertension.
• These findings may offer potential targets for developing sex-specific therapies for pulmonary hypertension.