Abstract

Objective This study investigated the mechanism of miR-296-5p in hypertensive stroke.Methods Ten patients with acute stroke and ten healthy volunteers were selected. EPCs were isolated and transfected, followed by assessment of cell activities. A mouse middle cerebral artery occlusion (tMCAO) model was established, and neural function deficits were evaluated using neural function score, forelimb placement test, and balance beam walking test. ACE2 and Mas receptor expression were assessed by TUNEL staining and immunohistochemical analysis. Serum Ang-(1-7) levels were measured using an ELISA kit. miR-296-5p, ACE2, and Mas were detected by RT-qPCR. The binding relationship between miR-296-5p and ACE2 was verified by dual luciferase assay and FISH.Results miR-296-5p expression was elevated in the peripheral blood of stroke patients. Lower HDL-C levels were associated with higher hemorrhagic volume, increased NIHSS score, and elevated miR-296-5p expression. miR-296-5p expression was also increased in brain tissue of tMCAO mice. Knockdown of miR-296-5p increased neuron numbers, indicating enhanced survival and reduced apoptosis. The decrease in Ang-(1-7) following miR-296-5p knockdown may reflect a feedback mechanism involving ACE2 regulation. Additionally, miR-296-5p targeted ACE2 expression, which may indirectly regulate Mas transcription through signaling pathways involved in neuroinflammation and ischemic injury. Overexpression of ACE2 reduced the effect of miR-296-5p knockdown on neural repair in tMCAO mice.Conclusion Serum miR-296-5p is a highly predictive marker for stroke prognosis. miR-296-5p alleviates hypertensive stroke by inhibiting Edn1 through ACE2.