Quercetin conjugated PSC-derived exosomes to inhibit intimal hyperplasia via modulating the ERK, Akt, and NF-κB signaling pathways in the rat carotid artery post balloon injury

The primary challenge in percutaneous coronary interventions for vascular restenosis is the occurrence of restenosis, which is defined by the excessive proliferation of neointimal tissue. Herein, our research team suggests that exosomes obtained from PSC, when paired with quercetin (Q@PSC-E), successfully reduce neointimal hyperplasia in a Sprague-Dawley rat model. Furthermore, the physical properties of the synthesized Q@PSC-E were examined using UV–vis, DLS, and FT-IR characterization techniques. The rats were subjected to balloon injury (BI) utilizing a 2-Fr Fogarty arterial embolectomy balloon catheter. Intimal hyperplasia and the degree of VSMC proliferation were evaluated using histological analysis in the rat groups that received a dosage of Q@PSC-E at 30 mg/kg/d. Significantly, Q@PSC-E inhibited cell proliferation through a pathway that does not include lipoxygenase, as demonstrated by [3H] thymidine incorporation, MTT, and flow cytometry studies. Additionally, the data indicate that Q@PSC-E hinders cell proliferation by targeting particular events that promote cell growth, including the activation of Akt and NF-κB, disruption of cell-cycle progression and also obstructs the ERK signaling pathway. In vascular restenosis, the primary limitation of percutaneous coronary interventions is restenosis, typified by the proliferation of neointimal tissue. Herein, our research team posits that exosomes derived from PSC, combined with quercetin (Q@PSC-E), effectively mitigate neointimal hyperplasia in a Sprague-Dawley rat model. Moreover, the physical characterization of Q@PSC-E was analyzed using UV–vis, DLS, and FT-IR spectroscopy. The balloon injury (BI) in the rats was induced using 2-Fr Fogarty arterial embolectomy balloon catheter. In the rat groups treated with Q@PSC-E (30 mg/kg/d), intimal hyperplasia and the extent of VSMC proliferation were assessed through histopathological analysis. Notably, Q@PSC-E curtailed cell proliferation through a lipoxygenase-independent route, as evidenced by [3H] thymidine incorporation, MTT, and flow cytometry analyses. Additionally, data reveal that Q@PSC-E impedes cell proliferation through specific proliferative events, encompassing Akt and NF-κB activations and the interruption of cell-cycle progression. Following this, it also hinders the ERK signaling pathway. [Display omitted] •Generation of high oxidant species attenuates intimal hyperplasia in balloon injury.•Herein a novel quercetin flavonoid conjugated PSC-e