Cell-autonomous and non-cell-autonomous effects of arginase-II on cardiac aging

• DOI: 10.7554/elife.94794
• Publication Date: 2024-04-02T17:25:05Z
• Authors: Duilio M. Potenza; Xin Cheng; Guillaume Ajalbert; Andrea Brenna; Marie-Noelle Giraud; Aurelien Frobert; Stephane Cook; Kirsten D. Mertz; Zhihong Yang; Xiu-Fen Ming
• Keywords: Cardiac cell

Aging is a predominant risk factor for heart disease. reveals low-grade chronic inflammation, cell apoptosis, cardiac fibrosis, and increased vulnerability to ischemic injury. The underlying molecular mechanisms responsible the aging phenotype its susceptibility injury are far from being fully understood. Although previous literature reports role of mitochondrial enzyme arginase-II (Arg-II) in development failure, contradictory results reported no systematic analysis cellular expression localization Arg-II has been performed. Whether how participates still unknown. In this study, we demonstrate, our surprise, that not expressed cardiomyocytes aged mice human patients, but upregulated non-myocytes heart, including macrophages, fibroblasts, endothelial cells. Mice with genetic deficiency arg-ii ( -/- ) protected age-associated myocyte interstitial perivascular endothelial-mesenchymal transition (EndMT), Further experiments show mediates IL-1β release macrophages old mice, contributing above-described phenotype. addition, enhances reactive oxygen species (mtROS) activates fibroblasts inhibited by inhibition mtROS. Thus, study demonstrates non-cell-autonomous effect on cardiomyocytes, cells mediated as well cell-autonomous through mtROS