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. Overall design: We crossed WT and heterozygous mice to have littermate controls with the correct genotypes. When the littermates reached 12 weeks old, they recieved 1 g/L of L-NAME in their drinking water for 8 weeks. At the end of their treatment, their whole aortas were extracted, and either (1) subjected to bulk RNA sequencing, or (2) single cell suspension was created, and subjected to 10x genomics single cell workflow. Our bulk RNA-seq experimental group had 6 biological replicates: Serpine1TA700/+ (3 males and 3 females). Our control group had biological replicates 6 Serpine1+/+ aortas (3 males and 3 females) Our scRNA-seq experimental group had 4 biological replicates: Serpine1TA700/+ (2 males and 2 females). Our control group had biological replicates 6 Serpine1+/+ aortas (3 males and 3 females)