Inhibition of extracellular matrix production and remodeling by doxycycline in smooth muscle cells

Abstract

Alterations in the extracellular matrix (ECM) production and remodeling of smooth muscle cells (SMCs) have been implicated in processes related to the differentiation in atherosclerosis. Due to the anti-atherosclerotic properties of the tetracyclines, we aimed to investigate whether cholesterol supplementation changes the effect of doxycycline over the ECM proteins synthesis and whether isoprenylated proteins and Rho A protein activation are affected. SMC primary culture isolated from chicks exposed to atherogenic factors in vivo (a cholesterol-rich diet, SMC-Ch), comparing it with control cultures isolated after a standard diet (SMC-C). After treatment with 20 nM doxycycline, [H]-proline and [H]-mevalonate incorporation were used to measure the synthesis of collagen and isoprenylated proteins, respectively. Real-time PCR was assessed to determine col1a2, col2a1, col3a1, fibronectin, and mmp2 gene expression and the pull-down technique was applied to determine the Rho A activation state. A higher synthesis of collagens and isoprenylated proteins in SMC-Ch than in SMC-C was determined showing that doxycycline inhibits ECM production and remodeling in both SMC types of cultures. Moreover, preliminary results about the effect of doxycycline on protein isoprenylation and Rho A protein activation led us to discuss the possibility that membrane G-protein activation pathways could mediate the molecular mechanism.

Effect of minocycline on the left ventricular function following ST-elevation myocardial infarction treated by primary percutaneous coronary intervention

“…Unlike doxycycline, which has been shown to improve cardiac remodeling in several studies [ 5 , 9 , 19 , 20 ], there are very few studies regarding the use of minocycline for the inhibition of MMP activation and, thereby, cardiac remodeling. One experimental study showed that minocycline could protect the adult rat cardiac myocytes against simulated ischemia-reperfusion injury by inhibiting poly (ADP-ribose) polymerase-1 [ 21 ].…”

Pro-Healing Nanomatrix-Coated Stent Analysis in an In Vitro Vascular Double-Layer System and in a Rabbit Model

“…Furthermore, it was reported that in some cases, calcification maybe also related to vascular remodeling, which could ECM remodeling and even restenosis. , We evaluated three genes (MMP-2, COL3A1, and COL17A1) that are involved with ECM remodeling. MMP-2 is one member of the matrix metalloproteinase family strongly related to ECM degradation, leading to plaque instability and rupture. − Figure D shows that PA-YKNO coating could significantly reduce MMP-2 expression. Additionally, COL3A1 and COL17A1 are associated with ECM remodeling leading to restenosis.…”

Threat Memory Reminder Under Matrix Metalloproteinase 9 Inhibitor Doxycycline Globally Reduces Subsequent Memory Plasticity

“…More tentatively, it is also possible that the effects of MMP on memory are not (only) conferred via LTP but via other mechanisms, including the configuration of extracellular matrix. Indeed, doxycycline affects extracellular matrix structure (Palomino-Morales et al, 2016), and different structural components of the matrix are suggested to impact on memory (Gogolla et al, 2009; Tsien, 2013; Happel et al, 2014; Banerjee et al, 2017). The turnaround time of the extracellular matrix is much longer than that of individual proteins (Tsien, 2013), thus explaining a long-lasting impact of doxycycline treatment.…”