| First Author | Cavallero S | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 7 | Pages | eadj7481 |
| PubMed ID | 38354249 | Mgi Jnum | J:350110 |
| Mgi Id | MGI:7594989 | Doi | 10.1126/sciadv.adj7481 |
| Citation | Cavallero S, et al. (2024) Exercise mitigates flow recirculation and activates metabolic transducer SCD1 to catalyze vascular protective metabolites. Sci Adv 10(7):eadj7481 |
| abstractText | Exercise promotes pulsatile shear stress in the arterial circulation and ameliorates cardiometabolic diseases. However, exercise-mediated metabolic transducers for vascular protection remain under-investigated. Untargeted metabolomic analysis demonstrated that wild-type mice undergoing voluntary wheel running exercise expressed increased endothelial stearoyl-CoA desaturase 1 (SCD1) that catalyzes anti-inflammatory lipid metabolites, namely, oleic (OA) and palmitoleic acids (PA), to mitigate NF-kappaB-mediated inflammatory responses. In silico analysis revealed that exercise augmented time-averaged wall shear stress but mitigated flow recirculation and oscillatory shear index in the lesser curvature of the mouse aortic arch. Following exercise, endothelial Scd1-deleted mice (Ldlr(-/-) Scd1(EC-/-)) on high-fat diet developed persistent VCAM1-positive endothelium in the lesser curvature and the descending aorta, whereas SCD1 overexpression via adenovirus transfection mitigated endoplasmic reticulum stress and inflammatory biomarkers. Single-cell transcriptomics of the aorta identified Scd1-positive and Vcam1-negative endothelial subclusters interacting with other candidate genes. Thus, exercise mitigates flow recirculation and activates endothelial SCD1 to catalyze OA and PA for vascular endothelial protection. |
