Fig. 3.

Local RAS-driven model for MPS cardiac disease. a IDUA gene architecture and X indicates a gene mutation resulting in loss of IDUA enzymatic activity. b In the aorta, GAG accumulation results in upregulation of multiple genes including cathepsins that are capable of converting Ang I to Ang II. Ang II exerts its pathological effects through the type I angiotensin receptor (AT1R) that results in upregulation of MMPs and diminished ACE2. ARB shunts the Ang II to the AT2R through which beneficial effects (increased ACE2 and decreased MMP gene expression) are mediated. The structural benefits are an aorta with a smaller size, normalized shortening fraction, and less thickening of the chambers (observed by decreased LVID and LVIS)