Cardiovascular LRP1 expression varies by anatomical site, with selective age- and sex-associated changes in human...

Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor implicated in atherosclerosis, arterial dissection, and vascular disease, with roles in lipid handling, extracellular matrix turnover, growth factor signaling, and vascular homeostasis. Although tissue-specific roles of LRP1 have been described, whether cardiovascular LRP1 expression varies by age, sex, and vascular bed remains unclear. Here, we analyzed publicly available human transcriptomic datasets to define the cardiovascular expression landscape of LRP1 across tissues, demographic strata, and cell populations. Genotype-Tissue Expression-derived data showed that vascular LRP1 expression differed significantly between the aorta, coronary artery, and tibial artery, with the highest expression in the aorta, where levels were 30% higher than coronary artery and 50% higher than tibial artery. In the heart, atrial LRP1 expression was approximately twofold higher than in the left ventricle. Among these five cardiovascular tissues, only the aorta showed sexual dimorphism, with 7.4% higher LRP1 expression in females than males. Tibial artery was the only tissue in which LRP1 expression changed significantly with age, doubling over female adulthood (adjusted P = 0.0019) and increasing 40% in male adulthood (adjusted P = 0.0284). Single-cell analyses of human heart and arterial datasets showed prominent LRP1 expression in adipocytes, fibroblasts, macrophages, and smooth muscle cells, indicating that tissue-level patterns reflect nonuniform expression across vascular and stromal cell populations. Together, these data indicate that cardiovascular LRP1 expression is not static, but can vary by anatomical and demographic context. This work establishes a baseline for interpreting LRP1-related mechanisms in vascular and cardiac disease.NEW & NOTEWORTHY Recent work has highlighted tissue-specific functional roles for Low-density lipoprotein receptor-related protein 1 (LRP1), but its cardiovascular expression landscape has not been systematically defined. Here, we show that human cardiovascular LRP1 expression varies between vascular beds, with sex and age selectively influencing expression, underscoring the importance of anatomical and demographic context in studies of LRP1 biology.