The pro-aging and rejuvenating effects of young and aged perivascular adipose tissues on endothelial function and inflammation.

Abstract

Aging is considered as an independent risk factor for cardiovascular diseases. Common hallmarks of vascular aging include endothelial dysfunction, vascular inflammation, elevated oxidative stress, and telomere dysfunction. Perivascular adipose tissue (PVAT) is the local aggregate of adipose tissue surrounding the vascular bed, serving as a critical regulator of vascular function via either paracrine or endocrine manners. Aging-dependent malfunction of adipose tissues increases the risk of cardiometabolic diseases. Aging was previously shown to attenuate the anticontractile effect of PVAT in rodent arteries. Therefore, this study sought to understand whether aged and young PVAT promote and retard vascular aging in young and aged mice. PVAT-free aortas from aged and young mice were co-cultured with aortic PVAT from young and aged donor mice for 48 h, respectively. Endothelium-dependent relaxations (EDRs) in mouse aortas were determined by wire myography. Aged PVAT co-culture impaired endothelial function in the aortas of young mice, while young PVAT co-culture slightly alleviated endothelial dysfunction in aged mice. Aged PVAT co-culture induced vascular oxidative stress and inflammation, impaired telomere function, and suppressed AMPK/SIRT1 signaling in young mouse aortas. Conversely, these detrimental effects were partially reversed by young PVAT co-culture in aged mouse aortas. We further showed that these pro-aging and rejuvenating effects of PVAT were partially mediated by growth differentiation factor 15 (GDF15) and inflammatory cytokines. These findings highlight a substantial role of PVAT in modulating endothelial function and vascular aging, implying adipose-vascular axis as potential intervention target against cardiovascular aging and diseases.