MicroRNA miR-29b regulates diabetic aortic remodeling and stiffening

Abstract

Patients with type 2 diabetes (T2D) are threatened by excessive cardiovascular morbidity and mortality. While accelerated arterial stiffening may represent a critical mechanistic factor driving cardiovascular risk in T2D, specific therapies to contain the underlying diabetic arterial remodeling have been elusive. The present translational study investigates the role of microRNA-29b (miR-29b) as a driver and therapeutic target of diabetic aortic remodeling and stiffening. Using a murine model (db/db mice), as well as human aortic tissue samples, we find that diabetic aortic remodeling and stiffening is associated with medial fibrosis, as well as fragmentation of aortic elastic layers. miR-29b is significantly downregulated in T2D and miR-29b repression is sufficient to induce both aortic medial fibrosis and elastin breakdown through upregulation of its direct target genes COL1A1 and MMP2 thereby increasing aortic stiffness. Moreover, antioxidant treatment restores aortic miR-29b levels and counteracts diabetic aortic remodeling. Concluding, we identify miR-29b as a comprehensive—and therefore powerful—regulator of aortic remodeling and stiffening in T2D that moreover qualifies as a (redox-sensitive) target for therapeutic intervention.

Integrated Analysis of lncRNA–miRNA–mRNA Regulatory Network in Rapamycin-Induced Cardioprotection against Ischemia/Reperfusion Injury in Diabetic Rabbits

“…Pretreatment of cardiac fibroblast cells with miR-29b-3p mimics abrogated TGF-β1-induced fibroblast activation, cell proliferation, and reduced the expression of collagen I, collagen III, α-SMA, MMP2, and MMP9 protein [106]. miR-29b can regulate remodeling and stiffening of the aortic valve in db/db diabetic mice [107]. The reduction in the level of miR-29b was attributed to the abundance of expression of its target genes Col1a1 and Mmp2.…”

Expression Profiles and Bioinformatic Analysis of Circular RNAs in Db/Db Mice with Cardiac Fibrosis

“…Previous research has shown that miR-29b is remarkably downregulated in db/db mice. 31 A recent study demonstrated that miR-29b upregulation could inhibit cardiac fibrosis in CFs and in a mouse myocardial infarction model. 32 In the present study, the upregulated circRNA_41535 and circRNA_20422 in DCM mice have binding sites with miR-29b-2-5p.…”

Biogénesis de miARN y su papel como biomarcadores en la detección de la nefropatía diabética

“…Estos factores inductores también son regulados por miARN. Por lo tanto, es razonable pensar que la regulación a la baja de algunos miARN permita el incremento de estos inductores, favoreciendo el desarrollo de la ND, como se muestra en la tabla 2 25,[35][36][37][38][39][40] . Se ha reportado que en modelos murinos con ND, miR-488 regula la expresión de TGF-β, el cual es un fuerte factor fibrótico que se expresa principalmente en riñón y que se distribuye abundantemente en glomérulos y túbulos renales, participando en el proceso patológico de la fibrosis renal, sugiriendo que miR-488 podría ser una nueva diana terapéutica para ND 41 .…”