miR-127-3p as a potential regulator of human coronary artery smooth muscle cell processes and their molecular pathways in vascular remodelling

Abstract

Pathological vascular remodelling arises from abnormal behaviour of SMCs, with miRs acting as key modulators. This thesis identifies a previously uncharacterized, context-dependent role for miR-127-3p in vascular remodelling. miR-127-3p is dynamically regulated in mouse models of atherosclerosis and restenosis and displays conservation across species. In human coronary artery SMCs (HCASMCs), miR-127-3p is present in the non-senescent (non-sen) and replicative-senescent (rep-sen) states. Gain-of-function experiments show that miR-127-3p suppresses proliferation in both contexts, while exerting opposite effects on migration: it reduces migration in non-sen cells but enhances it in rep-sen cells. Targets of miR-127-3p were identified. The miR consistently downregulates mTOR, while AXL is selectively upregulated in non-sen cells. Although miR-127-3p does not alter senescence itself, it promotes the production of ROS and pro-inflammatory signalling pathways in non-sen cells. These results position miR-127-3p as a regulator of HCASMCs that links growth control, migration, and inflammation in vascular remodelling.