Activation of the STAT3/microRNA‐21 pathway participates in angiotensin II‐induced angiogenesis

Abstract

Angiotensin II (AngII) facilitates angiogenesis that is associated with the continuous progression of atherosclerotic plaques, but the underlying mechanisms are still not fully understood. Several microRNAs (miRNAs) have been shown to promote angiogenesis; however, whether miRNAs play a crucial role in AngII‐induced angiogenesis remains unclear. This study evaluated the functional involvement of miRNA‐21 (miR‐21) in the AngII‐mediated proangiogenic response in human microvascular endothelial cells (HMECs). We found that AngII exerted a proangiogenic role, indicated by the promotion of proliferation, migration, and tube formation in HMECs. Next, miR‐21 was found to be upregulated in AngII‐treated HMECs, and its specific inhibitor potently blocked the proangiogenic effects of AngII. Subsequently, we focused on the constitutive activation of STAT3 in the AngII‐mediated proangiogenic process. Bioinformatic analysis indicated that STAT3 acted as a transcription factor initiating miR‐21 expression, which was verified by ChIP‐PCR. A reporter assay further identified three functional binding sites of STAT3 in the miR‐21 promoter region. Moreover, phosphatase and tensin homolog (PTEN) was recognized as a target of miR‐21, and STAT3 inhibition restored AngII‐induced reduction in PTEN. Similarly, the STAT3/miR‐21 axis was shown to mediate AngII‐provoked angiogenesis in vivo, which was demonstrated by using the appropriate inhibitors. Our data suggest that AngII was involved in proangiogenic responses through miR‐21 upregulation and reduced PTEN expression, which was, at least in part, linked to STAT3 signaling. The present study provides novel insights into AngII‐induced angiogenesis and suggests potential treatment strategies for attenuating the progression of atherosclerotic lesions and preventing atherosclerosis complications.

Low‐intensity Pulsed Ultrasound Ameliorates Angiotension Ii-induced Cardiac Fibrosisbyalleviating Inflammation via a Caveolin-1-dependent Pathway

“…Vascular endothelial growth factor (VEGF) is crucial in compensated angiogenesis associated with maintaining cardiac function ( [61]). AngII and LIPUS irradiation have been reported to induce endothelium-derived angiogenesis by different mechanisms ( [18,62]), which was in agreement with our results that increased protein expression of VEGF was found in mice hearts after AngII and/or LIPUS treatment. Given that caveolin-1 is highly expressed in the endothelium ( [63]), the above reasons may explain the increased caveolin-1 expression in heart tissues in the model group.…”

circRNA‑0006896‑miR1264‑DNMT1 axis plays an important role in carotid plaque destabilization by regulating the behavior of endothelial cells in atherosclerosis

“…UA-Exos influence the circRNA-0006896-miR-1264-DNMT1 axis in HUVECs. A previous study reported that HUVEC proliferation and migration are important events that induce plaque destabilization (23,24). The signaling molecules carried by exosomes may affect the biological behavior of target cells in the microenvironment (25).…”

STAT3 Regulates miR-384 Transcription During Th17 Polarization

“…Mechanistically, p-STAT3 binds to the promoter region of miR-199a-2 for regulation (Zhou et al, 2019). Three functional binding sites of STAT3 in the Mir21 promoter region mediate angiogenesis (Chen et al, 2019). During Th17 polarization, IL-6-activated STAT3 has particularly important roles in the expression of Rorγt, a Th17 lineage marker.…”