miRNA‑378a‑5p attenuates the development of abdominal aortic aneurysm via ABLIM1‑MKL1 signaling pathways

Abdominal aortic aneurysm (AAA) is a fatal cardiovascular disease with no effective drug treatment currently available. The aberrant expression levels of microRNAs (miRNAs or miRs) contribute to AAA pathogenesis. In the present study, miRNA microarray analysis was performed to screen for differentially expressed miRNAs in the aortas of AAA mice compared with those in control mice, and to clarify the role and mechanism of miRNA‑378a‑5p (miR‑378a‑5p) in the AAA development. A comprehensive miRNA microarray analysis was conducted to screen for differentially expressed miRNAs in the aortas of AAA mice and control mice. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detect the expression levels of miR‑378a‑5p in the serum and aortas of patients with AAA and mice. To clarify the role of miR‑378a‑5p in the AAA development in vivo, miR‑378a‑5p antagomir and angomir were administered to ApoE‑/‑ mice using tail venous injection, followed by Angiotensin II (Ang II) infusion. Next, the role of miR‑378a‑5p in the phenotypic switching and migration of vascular smooth muscle cells (VSMCs) was examined in vivo and in vitro. Mechanistically, the targets of miR‑378a‑5p were identified by bioinformatics analysis, luciferase assay, RT‑qPCR and western blotting. Co‑immunoprecipitation assay combined with mass spectrometry were carried out for excavating potential downstream effectors. The expression of miR‑378a‑5p was decreased in the serum and aortas of patients with AAA (aortic dissection) and mice, and tumor necrosis factor‑α‑treated VSMCs. In vivo, the antagomir‑378a‑5p aggravated AAA formation, as evidenced by a larger maximal aortic diameter and greater medial elastin degradation than in control mice. miR‑378a‑5p angomir had the opposite effect. In vitro, miR‑378a‑5p overexpression significantly promoted the contraction ability and suppressed the migration of VSMCs, whereas miR‑378a‑5p knockdown inhibited the contraction ability and increased the migration of VSMCs. Mechanistically, it was identified that miR‑378a‑5p played a protective role in AAA development by regulating actin‑binding LIM protein 1 (ABLIM1)‑megakaryoblastic leukemia 1 (MKL1) pathway. miR‑378a‑5p exerts protective effects against AAA by maintaining VSMCs homeostasis via the ABLIM1‑MKL1 pathway. Therefore, targeting miR‑378a‑5p may be an attractive therapeutic strategy for AAA treatment.