Metformin inhibited cardiac fibrosis induced by pressure overload in vivo and inhibited collagen synthesis in CFs probably via inhibition of the TGF-beta(1)-Smad3 signalling pathway. These findings provide a new mechanism for the cardioprotective effects of metformin.

As a novel type of CM to FB communication, membrane nanotubes observed in vitro and in vivo provide structural and functional connectivity between CMs and FBs over long distances.

The activity of heterogeneous photocatalytic H2O2 activation in Fenton‐like processes is closely related to the local electron density of reaction centre atoms. However, the recombination of electron‐hole pairs arising from random charge transfer greatly restricts the oriented electron delivery to active center. Here we show a defect engineered iron single atom photocatalyst (Fe1‐Nv/CN, single Fe atoms dispersed on carbon nitride with abundant nitrogen vacancies) for the activation of H2O2 under visible light irradiation. Based on DFT calculations and transient absorption spectroscopy results, the engineered nitrogen vacancies serve as the electron trap sites, which can directionally drive the electrons to concentrate on Fe atoms. The formation of highly concentrated electrons density at Fe sites significantly improves the H2O2 conversion efficiency. Therefore, the optimized single atom catalyst exhibiting a higher ciprofloxacin degradation activity, which was up to 18 times that of pristine CN.

Rationale: Aortic aneurysm is a life-threatening cardiovascular disorder caused by the predisposition for dissection and rupture. Genetic studies have proved the involvement of the transforming growth factor-β (TGF-β) pathway in aortic aneurysm. Smad4 is the central mediator of the canonical TGF-β signaling pathway. However, the exact role of Smad4 in smooth muscle cells (SMCs) leading to the pathogenesis of aortic aneurysms is largely unknown. Objective: To determine the role of smooth muscle Smad4 in the pathogenesis of aortic aneurysms. Methods and Results: Conditional gene knockout strategy combined with histology and expression analysis showed that Smad4 or TGF-β receptor type II deficiency in SMCs led to the occurrence of aortic aneurysms along with an upregulation of cathepsin S and matrix metallopeptidase-12, which are proteases essential for elastin degradation. We further demonstrated a previously unknown downregulation of matrix metallopeptidase-12 by TGF-β in the aortic SMCs, which is largely abrogated in the absence of Smad4. Chemotactic assay and pharmacologic treatment demonstrated that Smad4-deficient SMCs directly triggered aortic wall inflammation via the excessive production of chemokines to recruit macrophages. Monocyte/macrophage depletion or blocking selective chemokine axis largely abrogated the progression of aortic aneurysm caused by Smad4 deficiency in SMCs. Conclusions: The findings reveal that Smad4-dependent TGF-β signaling in SMCs protects against aortic aneurysm formation and dissection. The data also suggest important implications for novel therapeutic strategies to limit the progression of the aneurysm resulting from TGF-β signaling loss-of-function mutations.