Ameliorative effect of allicin on vascular calcification via inhibiting endoplasmic reticulum stress

Abstract

Objectives Vascular calcification (VC) is an independent predictor for cardiovascular events and mortality. However, there are currently no effective methods to reverse or prevent it. The present study aimed to determine the ameliorative effect of allicin on VC. Methods VC model of rats was induced by high-dose vitamin D3, which was valued by Alizarin Red staining, calcium contents, and alkaline phosphatase in the aorta. Systolic blood pressure, pulse pressure, and pulse wave velocity were measured to determine aortic stiffness. Protein levels were detected by Western blot. Results Allicin treatment rescued aortic VC and stiffness. The increased protein levels of RUNX2 and BMP2, two markers of osteoblastic phenotype of vascular smooth muscle cells, in the calcified aorta were attenuated by allicin, whereas the decreased levels of calponin and SM22α induced by calcification were improved. Allicin treatment significantly attenuated the increased protein levels of GRP78, GRP94, and CHOP, which are key markers of endoplasmic reticulum stress, in the calcified aorta. The activation of PERK/eIF2α/ATF4 cascades was also prevented by allicin. Conclusions Allicin could ameliorate aortic VC and stiffness. The ameliorative effect of allicin on VC might be mediated by inhibiting PERK/eIF2α/ATF4 cascades. Our results might provide a new proof for VC treatment.

D-box-binding protein alleviates vascular calcification in rats with chronic kidney disease by activating microRNA-195-5p and downregulating cyclin D1

“…We found that overexpression of DBP in CKD rats led to a reduction in the expression of RUNX2 and BMP2. Both RUNX2 and BMP2 serve as indicators of the osteoblastic phenotype in VSMCs and are often highly expressed in calcified aortas [ 27 ]. Therefore, the reduced levels of RUNX2 and BMP2 suggested a reduction in VC.…”

Exosomal miR-129 and miR-342 derived from intermittent hypoxia-stimulated vascular smooth muscle cells inhibit the eIF2α/ATF4 axis from preventing calcified aortic valvular disease

“…Intriguingly, induced ATF4 expression due to increased stearate could contribute to enhanced osteoblastic differentiation as well as mineralization of VSMCs, involved with the activated PERK‐eIF2α pathway, thereby augmenting vascular calcification (Masuda et al 2012). Inhibition of PERK/eIF2α/ATF4 cascades due to Allicin treatment can attenuate aortic vascular calcification and stiffness (Wang et al 2022). Furthermore, inactivated PERK‐eIF2α‐ATF4 pathway due to pre‐culture of VSMCs using terpinen‐4‐ol or a SIRT1 agonist ameliorates vascular calcification (Zhang et al 2021a, b).…”

Prioritization of Candidate Biomarkers for Degenerative Aortic Stenosis through a Systems Biology-Based In-Silico Approach

“…As all three branches of the UPR, the protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase and endonuclease-1α (IRE1α), and activating transcription factor (ATF), are activated during bone formation to regulate expression of osteogenic genes, it is crucial to elucidate the role of endoplasmin in valve calcification [42][43][44][45][46]. Importantly, elevated levels of endoplasmin have been found in calcified vascular smooth muscle cells [47] and in the calcified aorta [48,49], consistent with our results.…”