Identification of Disease-Relevant, Sex-Based Proteomic Differences in iPSC-Derived Vascular Smooth Muscle Cells.
Publication Year:
2024
PubMed ID:
39796045
Funding Grants:
Public Summary:
Heart and blood vessel diseases often affect men and women differently, but we don’t fully understand why. This study used stem cells from healthy men and women to create blood vessel muscle cells in the lab and compared their proteins. They found important differences linked to energy use and cell adhesion that could explain how sex affects blood vessel health. Interestingly, some of these differences involved genes not only on sex chromosomes but also on regular chromosomes. These findings show that lab-grown blood vessel cells can help us study sex-specific heart disease and may lead to better, tailored treatments for men and women.
Scientific Abstract:
The prevalence of cardiovascular disease varies with sex, and the impact of intrinsic sex-based differences on vasculature is not well understood. Animal models can provide important insights into some aspects of human biology; however, not all discoveries in animal systems translate well to humans. To explore the impact of chromosomal sex on proteomic phenotypes, we used iPSC-derived vascular smooth muscle cells from healthy donors of both sexes to identify sex-based proteomic differences and their possible effects on cardiovascular pathophysiology. Our analysis confirmed that differentiated cells have a proteomic profile more similar to healthy primary aortic smooth muscle cells than iPSCs. We also identified sex-based differences in iPSC-derived vascular smooth muscle cells in pathways related to ATP binding, glycogen metabolic process, and cadherin binding as well as multiple proteins relevant to cardiovascular pathophysiology and disease. Additionally, we explored the role of autosomal and sex chromosomes in protein regulation, identifying that proteins on autosomal chromosomes also show sex-based regulation that may affect the protein expression of proteins from autosomal chromosomes. This work supports the biological relevance of iPSC-derived vascular smooth muscle cells as a model for disease, and further exploration of the pathways identified here can lead to the discovery of sex-specific pharmacological targets for cardiovascular disease.