Single Cell RNA Sequencing of C57BL6 mouse whole aortas after 8 weeks of L-NAME treatment

Humans with a heterozygous loss-of-function SERPINE1 variant exhibit protection against biological aging and cardiometabolic dysfunction. Here, we reverse engineered a mouse model mimicking the human mutation (Serpine1TA700/+) and compared cardiovascular responses with wild-type littermates. Under L-NG-Nitro-arginine methyl ester (L-NAME)-induced vascular stress, Serpine1TA700/+ mice exhibited protection from systolic hypertension (SBP), preserved left ventricular diastolic function, and diminished aortic pulse wave velocity (PWV) compared to controls. Single cell transcriptomic analyses of Serpine1TA700/+ aortas, revealed a vascular-protective mechanism that involves the downregulation of extracellular matrix regulators Ccn1 and Itgb1.